Cases That Test Your Skills

History: An inpatient discovery

Ms. A, 20, presented to the emergency room with an exacerbation of asthma due to noncompliance with medications. A review of her systems and a physical exam revealed significant bilateral shortness of breath, wheezes, and rhonchi.

A single mother who lives with her two daughters, ages 5 and 2, Ms. A is 28 weeks pregnant with her third child. After receiving albuterol nebulizers for her asthma, she was admitted to the obstetrics and gynecology floor for monitoring of maternal and fetal status. There, a nursing staff member observed her eating baby powder.

The psychiatric team evaluated Ms. A and learned that, during her first pregnancy at age 15, she grew uncomfortable with her increased weight and started purging. Standing at 5 feet, 6 inches, Ms. A weighed as much as 220 during the pregnancy; her weight fell to 170 pounds after delivery. When she presented to us she lamented, “All of my friends are still thin.”

The stress of being a single teenage mother and going to school, combined with disgust over her physical appearance, provoked her purging. She did not think purging would help her lose weight but would prevent her from gaining more even as she ate as much as she wanted.

For 11 months after the birth of her first child, she purged three to four times daily. She could eat as many as five “value meals” within 2 to 3 hours at fast-food restaurants. Eating relaxed her and made her feel comfortable, but the frequency of purging escalated to five to six times daily and the vomiting was physically exhausting, painful, and caused esophageal damage.

At age 17, Ms. A became pregnant with her second child. In the first 2 to 3 months, she continued to eat large quantities of food but purged less often (two to three times daily).

One day in the third month of this pregnancy, Ms. A watched as her mother used medicated powder on her own child, and the powder's scent stimulated within Ms. A an urge to taste it. Before long Ms. A was eating the powder regularly and had stopped purging. She recalled purging only three times during the remaining 6 months of the pregnancy. The craving for powder replaced both her desire to vomit and the need to binge on food. She returned to regular binging and purging (once or twice weekly) after her second child was born, however.

In your view, which should be addressed first, the bulimia or the obsession with baby powder? Or should both be addressed in tandem?

Commentary

This case displays a form of adult pica for baby powder, which has only been described in the literature for pediatric pica.^1,2 She displays no cognitive deficits or psychological disorders (e.g., mental retardation, schizophrenia) that are commonly associated with pica.^3-6 Pregnancy, which is also common in pica, did exist in this patient and may provide some physiologic or psychological insight into the patient’s disorder.⁷ The patient’s bulimia nervosa, however, gives an unusual twist to this case.

In the 18th century, pica was classified together with bulimia simply as an erroneous or aberrant appetite (Box 1).⁸ Pica has been known to occur with—and can be a symptom of—bulimia and anorexia, but it is rarely cited.^8,10 As in other eating disorders, affected individuals are ashamed of their weight, body shape, and body image.¹³

Box 1

Comorbid bulimia and pica disorders tend to work together to accomplish a similar task: weight loss/control. Eating non-nutritive substances occupies space in the stomach, creating a sense of satiety without taking in calories. Therefore, this behavior acts as a substitute for binging in the patient with bulimia.¹⁴

One study identified eight themes associated with pica during pregnancy: keeping practices secret, singularity of the experience, extravagant means for obtaining the craved substance, fears for the effects on the fetus, yielding or not yielding to the cravings, use of the substances as medication, pica and lack of food intake, and sensory experiences other than taste.² All eight of these themes were present in Ms. A.

Evaluation: Needing more and more

By her third pregnancy, Ms. A’s obsession with powder started to take hold. She found it easier to conceal the purging from her partner, so she began purging more often (twice daily) to offset her cravings for the baby powder. Purging was a last resort for the patient and her only means of off-setting her desire for the powder, which relieved her urge to vomit. She ate baby powder throughout the day, even awaking two to three times at night to ingest a few spoonfuls.

Until she presented to us, Ms. A had followed a daily ritual. At 10:30 a.m., when the local drug store opens, she superficially tested the consistency of a certain brand of powder available on the shelves. She then purchased one case (six 14-ounce containers) of powder, went home and sampled each container, and rated them in quality from 1 to 6, with 1 being the bottle of powder she ate that day. The next morning, regardless of how many cases of powder were piled in her closet, she went to the drug store and repeated the process.

Ms. A felt comfortable eating the talc-based powder in her apartment and her mother’s house. She kept some baby powder in her desk at work, but she regularly took an hour-long lunch break to drive back to her apartment and satisfy her craving. She also carried powder in the car, tasting it while driving.

When asked how the powder made her feel, Ms. A replied: “Powder is like nothing else. It makes me feel content and at ease.” Whenever she was irritated, or if the children were frustrating her, she would take a spoonful of powder.

In the beginning, she consumed approximately one 14-ounce bottle per month. When she presented 28 weeks pregnant with her third child, she could not imagine life without baby powder. A spoonful satisfied her for only 5 to 10 minutes before she would desire more. No other substance quelled the cravings. She had tried edible substitutes such as confectioners sugar, cornstarch, and ice chips, but nothing offered the satisfaction she got from powder.

When she is unable to ingest powder, she develops a headache, begins to sweat, gets extremely anxious and irritable, cries profusely, and becomes depressed. If she is abstinent more than 2 days she is unable to sleep and becomes preoccupied with the powder. If powder is not available, she binges and induces vomiting to stifle her craving.

In the hospital she craved powder 2 days after it was removed from her access. She became extremely anxious and distressed. She then ordered as much food as possible so she could purge and forget about the powder.

How would you explain the patient’s psychopathological attraction to baby powder?

Commentary

Patients with pica typically express satisfaction from consuming non-nutrient substances (Box 2). Ms. A’s motive for eating the powder stemmed from what she perceived as its soothing properties.

Other reported cases have alluded to the sensation generated by the texture of soil or chalk in the mouth. Some of these patients also described the importance of the soil’s taste—i.e., particle size—as being second to its texture.¹² The desire to experience a certain texture, color, odor, and taste are important components in pica cravings.¹⁰

Box 2

Pica appears to meet the individual’s need for mental relaxation and sensory pleasure¹⁵ in much the same way that alcohol or drug abusers satisfy their intense desire for euphoria and relaxation. Scientists theorize that alcohol and drug abuse may be exacerbated by or result from a neurochemical imbalance. A similar hypothesis may explain this “variant” in pica patients.

Pregnant women often develop taste aversions for items that are potentially harmful to the developing fetus, such as alcohol and coffee. Expectant mothers may develop utter disgust and provocation of nausea toward items they enjoyed while not gravid. Aversions to foods and other items during pregnancy might be the consequence of homeostatic factors that have evolved as general feto-protective mechanisms.^16,17 The metabolic changes that accompany the gravid state might alter olfactory and taste sensitivity.¹⁷

If a pregnancy-related change in chemical balance can cause taste aversion, certainly a similar situation could evolve into pica. In laboratory rats, intraventricular injection of exogenous neuropeptide Y, a hormone with documented CNS activity, caused taste aversions and elicited geophagia.¹⁸

Ms. A’s ingestion of baby powder itself did not harm the fetus. Stephen Emery, MD, director of perinatal ultrasound at the Cleveland Clinic, notes that talc is inert and the powder’s perfumes probably are benign. He adds, however, that because the powder often has replaced real food, Ms. A placed her unborn child at risk via malnourishment.

Further evaluation: A ‘pleasant’ appearance

Ms. A’s medical history revealed chronic asthma since childhood and gastroesophageal reflux disease. According to her social history, she is dating the father of her expectant child. She has been smoking one pack of cigarettes per day for 2 years but says she does not drink alcohol and has never abused illicit drugs.

Her lab values were as follows (with normal ranges in parentheses): blood urea, 4 mg/dl (9-23); serum iron, 69 mg/dl (42-135); calcium 8.7 mg/dl (8.5-10.5); magnesium, 1.6 mg/dl (1.8-2.4); phosphate, 2.4 mg/dl (2.7-4.6); hemoglobin, 10.0 g/dl (12.0-14.0); hematocrit, 31.1% (37.0-47.0); mean corpuscular volume, 86.4 fl (81-99).

Ms. A appeared well-nourished, appropriately dressed, and well-groomed during our examination. She was alert, oriented and cooperative, and held a pleasant conversation with good eye contact. Her mood was depressed and anxious, and her affect was congruent. Speech was normal in rate, tone, and volume. Her thoughts were well organized and goal-directed. She denied suicidal ideation but had thoughts of harming her fetus. She denied any perceptual disturbances. No intellectual impairment was evident, and her insight and judgment were preserved.

What is the psychiatric diagnosis for this patient? Also, in your view, how likely is she to harm her fetus or her two children? How would you assess and manage that risk?

Commentary

The physiologic cause of pica may be metabolic disturbances in iron, zinc, calcium, potassium, lead, and magnesium.^10,19-22 Ice pica typically is associated with iron deficiency and low hemoglobin levels,^14,20,23,24 although other forms of pica have been linked to iron deficiency.^12,25 Some studies show iron deficiency in nearly half of patients who display ice pica;^20,26 correcting the iron deficiency relieves the cravings for the desired substances.^7,14 Scientists are split as to whether pica results in the deficiency of certain minerals or whether mineral deficiencies cause pica. Mineral deficiencies may alter appetite-regulating brain enzymes that can lead to these cravings.^7,10,11,23

Ms. A’s laboratory values demonstrated decreased hemoglobin, hematocrit, and magnesium levels. Magnesium replacement did not change her eating behavior. Her mild anemia may simply have been an effect of pregnancy.

Treatment: Confronting comorbid depression

Ms. A’s diagnosis was pica, bulimia nervosa-purging type, with comorbid depressive disorder NOS.

She was placed on the selective serotonin reuptake inhibitor sertraline, 12.5 mg/d. The dosage was increased gradually to 50 mg qd. Supportive psychotherapy was provided during the patient’s hospital course.

After her discharge, cognitive therapy was initiated. Ms. A was asked to keep a journal utilizing the “triple column technique,” through which she described a situation in one column, explained the symptoms or unwanted behaviors and emotions evoked by that situation in the second, and wrote down her thoughts in the third.

Ms. A was monitored for signs and symptoms of postpartum depression. After this careful assessment, in which two psychiatrists and the ob/gyn team participated, we concluded that the patient’s transient thoughts of harming her fetus had fully resolved.

Ms. A was educated about nutrition and healthy exercise, as well as birth control options. We also asked to see her as an outpatient.

In the ensuing months, Ms. A reported moderate depressive symptoms but described a significant decrease in her craving for, and consumption of, powder. She continued follow-up treatment with her physician at the women’s care center. Ms. A decided to stop taking sertraline after 2 months because she felt it was not helping her depression and was causing fatigue.

When we followed up after 6 months, Ms. A reported that she and her baby were doing well. She told us that her powder cravings had decreased markedly.

Related resources

• Alliance for Eating Disorders Awareness. www.eatingdisorderinfo.org
• Stein DJ, Bouwer C, van Heerden B. Pica and the obsessive spectrum disorders. S Afr Med J 1996; 86(12 suppl):1586-8, 1591-2.

Drug brand names

• Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article.

History: An inpatient discovery

Ms. A, 20, presented to the emergency room with an exacerbation of asthma due to noncompliance with medications. A review of her systems and a physical exam revealed significant bilateral shortness of breath, wheezes, and rhonchi.

A single mother who lives with her two daughters, ages 5 and 2, Ms. A is 28 weeks pregnant with her third child. After receiving albuterol nebulizers for her asthma, she was admitted to the obstetrics and gynecology floor for monitoring of maternal and fetal status. There, a nursing staff member observed her eating baby powder.

The psychiatric team evaluated Ms. A and learned that, during her first pregnancy at age 15, she grew uncomfortable with her increased weight and started purging. Standing at 5 feet, 6 inches, Ms. A weighed as much as 220 during the pregnancy; her weight fell to 170 pounds after delivery. When she presented to us she lamented, “All of my friends are still thin.”

The stress of being a single teenage mother and going to school, combined with disgust over her physical appearance, provoked her purging. She did not think purging would help her lose weight but would prevent her from gaining more even as she ate as much as she wanted.

For 11 months after the birth of her first child, she purged three to four times daily. She could eat as many as five “value meals” within 2 to 3 hours at fast-food restaurants. Eating relaxed her and made her feel comfortable, but the frequency of purging escalated to five to six times daily and the vomiting was physically exhausting, painful, and caused esophageal damage.

At age 17, Ms. A became pregnant with her second child. In the first 2 to 3 months, she continued to eat large quantities of food but purged less often (two to three times daily).

One day in the third month of this pregnancy, Ms. A watched as her mother used medicated powder on her own child, and the powder's scent stimulated within Ms. A an urge to taste it. Before long Ms. A was eating the powder regularly and had stopped purging. She recalled purging only three times during the remaining 6 months of the pregnancy. The craving for powder replaced both her desire to vomit and the need to binge on food. She returned to regular binging and purging (once or twice weekly) after her second child was born, however.

In your view, which should be addressed first, the bulimia or the obsession with baby powder? Or should both be addressed in tandem?

Commentary

This case displays a form of adult pica for baby powder, which has only been described in the literature for pediatric pica.^1,2 She displays no cognitive deficits or psychological disorders (e.g., mental retardation, schizophrenia) that are commonly associated with pica.^3-6 Pregnancy, which is also common in pica, did exist in this patient and may provide some physiologic or psychological insight into the patient’s disorder.⁷ The patient’s bulimia nervosa, however, gives an unusual twist to this case.

In the 18th century, pica was classified together with bulimia simply as an erroneous or aberrant appetite (Box 1).⁸ Pica has been known to occur with—and can be a symptom of—bulimia and anorexia, but it is rarely cited.^8,10 As in other eating disorders, affected individuals are ashamed of their weight, body shape, and body image.¹³

Box 1

Comorbid bulimia and pica disorders tend to work together to accomplish a similar task: weight loss/control. Eating non-nutritive substances occupies space in the stomach, creating a sense of satiety without taking in calories. Therefore, this behavior acts as a substitute for binging in the patient with bulimia.¹⁴

One study identified eight themes associated with pica during pregnancy: keeping practices secret, singularity of the experience, extravagant means for obtaining the craved substance, fears for the effects on the fetus, yielding or not yielding to the cravings, use of the substances as medication, pica and lack of food intake, and sensory experiences other than taste.² All eight of these themes were present in Ms. A.

Evaluation: Needing more and more

By her third pregnancy, Ms. A’s obsession with powder started to take hold. She found it easier to conceal the purging from her partner, so she began purging more often (twice daily) to offset her cravings for the baby powder. Purging was a last resort for the patient and her only means of off-setting her desire for the powder, which relieved her urge to vomit. She ate baby powder throughout the day, even awaking two to three times at night to ingest a few spoonfuls.

Until she presented to us, Ms. A had followed a daily ritual. At 10:30 a.m., when the local drug store opens, she superficially tested the consistency of a certain brand of powder available on the shelves. She then purchased one case (six 14-ounce containers) of powder, went home and sampled each container, and rated them in quality from 1 to 6, with 1 being the bottle of powder she ate that day. The next morning, regardless of how many cases of powder were piled in her closet, she went to the drug store and repeated the process.

Ms. A felt comfortable eating the talc-based powder in her apartment and her mother’s house. She kept some baby powder in her desk at work, but she regularly took an hour-long lunch break to drive back to her apartment and satisfy her craving. She also carried powder in the car, tasting it while driving.

When asked how the powder made her feel, Ms. A replied: “Powder is like nothing else. It makes me feel content and at ease.” Whenever she was irritated, or if the children were frustrating her, she would take a spoonful of powder.

In the beginning, she consumed approximately one 14-ounce bottle per month. When she presented 28 weeks pregnant with her third child, she could not imagine life without baby powder. A spoonful satisfied her for only 5 to 10 minutes before she would desire more. No other substance quelled the cravings. She had tried edible substitutes such as confectioners sugar, cornstarch, and ice chips, but nothing offered the satisfaction she got from powder.

When she is unable to ingest powder, she develops a headache, begins to sweat, gets extremely anxious and irritable, cries profusely, and becomes depressed. If she is abstinent more than 2 days she is unable to sleep and becomes preoccupied with the powder. If powder is not available, she binges and induces vomiting to stifle her craving.

In the hospital she craved powder 2 days after it was removed from her access. She became extremely anxious and distressed. She then ordered as much food as possible so she could purge and forget about the powder.

How would you explain the patient’s psychopathological attraction to baby powder?

Commentary

Patients with pica typically express satisfaction from consuming non-nutrient substances (Box 2). Ms. A’s motive for eating the powder stemmed from what she perceived as its soothing properties.

Other reported cases have alluded to the sensation generated by the texture of soil or chalk in the mouth. Some of these patients also described the importance of the soil’s taste—i.e., particle size—as being second to its texture.¹² The desire to experience a certain texture, color, odor, and taste are important components in pica cravings.¹⁰

Box 2

Pica appears to meet the individual’s need for mental relaxation and sensory pleasure¹⁵ in much the same way that alcohol or drug abusers satisfy their intense desire for euphoria and relaxation. Scientists theorize that alcohol and drug abuse may be exacerbated by or result from a neurochemical imbalance. A similar hypothesis may explain this “variant” in pica patients.

Pregnant women often develop taste aversions for items that are potentially harmful to the developing fetus, such as alcohol and coffee. Expectant mothers may develop utter disgust and provocation of nausea toward items they enjoyed while not gravid. Aversions to foods and other items during pregnancy might be the consequence of homeostatic factors that have evolved as general feto-protective mechanisms.^16,17 The metabolic changes that accompany the gravid state might alter olfactory and taste sensitivity.¹⁷

If a pregnancy-related change in chemical balance can cause taste aversion, certainly a similar situation could evolve into pica. In laboratory rats, intraventricular injection of exogenous neuropeptide Y, a hormone with documented CNS activity, caused taste aversions and elicited geophagia.¹⁸

Ms. A’s ingestion of baby powder itself did not harm the fetus. Stephen Emery, MD, director of perinatal ultrasound at the Cleveland Clinic, notes that talc is inert and the powder’s perfumes probably are benign. He adds, however, that because the powder often has replaced real food, Ms. A placed her unborn child at risk via malnourishment.

Further evaluation: A ‘pleasant’ appearance

Ms. A’s medical history revealed chronic asthma since childhood and gastroesophageal reflux disease. According to her social history, she is dating the father of her expectant child. She has been smoking one pack of cigarettes per day for 2 years but says she does not drink alcohol and has never abused illicit drugs.

Her lab values were as follows (with normal ranges in parentheses): blood urea, 4 mg/dl (9-23); serum iron, 69 mg/dl (42-135); calcium 8.7 mg/dl (8.5-10.5); magnesium, 1.6 mg/dl (1.8-2.4); phosphate, 2.4 mg/dl (2.7-4.6); hemoglobin, 10.0 g/dl (12.0-14.0); hematocrit, 31.1% (37.0-47.0); mean corpuscular volume, 86.4 fl (81-99).

Ms. A appeared well-nourished, appropriately dressed, and well-groomed during our examination. She was alert, oriented and cooperative, and held a pleasant conversation with good eye contact. Her mood was depressed and anxious, and her affect was congruent. Speech was normal in rate, tone, and volume. Her thoughts were well organized and goal-directed. She denied suicidal ideation but had thoughts of harming her fetus. She denied any perceptual disturbances. No intellectual impairment was evident, and her insight and judgment were preserved.

What is the psychiatric diagnosis for this patient? Also, in your view, how likely is she to harm her fetus or her two children? How would you assess and manage that risk?

Commentary

The physiologic cause of pica may be metabolic disturbances in iron, zinc, calcium, potassium, lead, and magnesium.^10,19-22 Ice pica typically is associated with iron deficiency and low hemoglobin levels,^14,20,23,24 although other forms of pica have been linked to iron deficiency.^12,25 Some studies show iron deficiency in nearly half of patients who display ice pica;^20,26 correcting the iron deficiency relieves the cravings for the desired substances.^7,14 Scientists are split as to whether pica results in the deficiency of certain minerals or whether mineral deficiencies cause pica. Mineral deficiencies may alter appetite-regulating brain enzymes that can lead to these cravings.^7,10,11,23

Ms. A’s laboratory values demonstrated decreased hemoglobin, hematocrit, and magnesium levels. Magnesium replacement did not change her eating behavior. Her mild anemia may simply have been an effect of pregnancy.

Treatment: Confronting comorbid depression

Ms. A’s diagnosis was pica, bulimia nervosa-purging type, with comorbid depressive disorder NOS.

She was placed on the selective serotonin reuptake inhibitor sertraline, 12.5 mg/d. The dosage was increased gradually to 50 mg qd. Supportive psychotherapy was provided during the patient’s hospital course.

After her discharge, cognitive therapy was initiated. Ms. A was asked to keep a journal utilizing the “triple column technique,” through which she described a situation in one column, explained the symptoms or unwanted behaviors and emotions evoked by that situation in the second, and wrote down her thoughts in the third.

Ms. A was monitored for signs and symptoms of postpartum depression. After this careful assessment, in which two psychiatrists and the ob/gyn team participated, we concluded that the patient’s transient thoughts of harming her fetus had fully resolved.

Ms. A was educated about nutrition and healthy exercise, as well as birth control options. We also asked to see her as an outpatient.

In the ensuing months, Ms. A reported moderate depressive symptoms but described a significant decrease in her craving for, and consumption of, powder. She continued follow-up treatment with her physician at the women’s care center. Ms. A decided to stop taking sertraline after 2 months because she felt it was not helping her depression and was causing fatigue.

When we followed up after 6 months, Ms. A reported that she and her baby were doing well. She told us that her powder cravings had decreased markedly.

Related resources

• Alliance for Eating Disorders Awareness. www.eatingdisorderinfo.org
• Stein DJ, Bouwer C, van Heerden B. Pica and the obsessive spectrum disorders. S Afr Med J 1996; 86(12 suppl):1586-8, 1591-2.

Drug brand names

• Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article.

History: An inpatient discovery

Ms. A, 20, presented to the emergency room with an exacerbation of asthma due to noncompliance with medications. A review of her systems and a physical exam revealed significant bilateral shortness of breath, wheezes, and rhonchi.

A single mother who lives with her two daughters, ages 5 and 2, Ms. A is 28 weeks pregnant with her third child. After receiving albuterol nebulizers for her asthma, she was admitted to the obstetrics and gynecology floor for monitoring of maternal and fetal status. There, a nursing staff member observed her eating baby powder.

The psychiatric team evaluated Ms. A and learned that, during her first pregnancy at age 15, she grew uncomfortable with her increased weight and started purging. Standing at 5 feet, 6 inches, Ms. A weighed as much as 220 during the pregnancy; her weight fell to 170 pounds after delivery. When she presented to us she lamented, “All of my friends are still thin.”

The stress of being a single teenage mother and going to school, combined with disgust over her physical appearance, provoked her purging. She did not think purging would help her lose weight but would prevent her from gaining more even as she ate as much as she wanted.

For 11 months after the birth of her first child, she purged three to four times daily. She could eat as many as five “value meals” within 2 to 3 hours at fast-food restaurants. Eating relaxed her and made her feel comfortable, but the frequency of purging escalated to five to six times daily and the vomiting was physically exhausting, painful, and caused esophageal damage.

At age 17, Ms. A became pregnant with her second child. In the first 2 to 3 months, she continued to eat large quantities of food but purged less often (two to three times daily).

One day in the third month of this pregnancy, Ms. A watched as her mother used medicated powder on her own child, and the powder's scent stimulated within Ms. A an urge to taste it. Before long Ms. A was eating the powder regularly and had stopped purging. She recalled purging only three times during the remaining 6 months of the pregnancy. The craving for powder replaced both her desire to vomit and the need to binge on food. She returned to regular binging and purging (once or twice weekly) after her second child was born, however.

In your view, which should be addressed first, the bulimia or the obsession with baby powder? Or should both be addressed in tandem?

Commentary

This case displays a form of adult pica for baby powder, which has only been described in the literature for pediatric pica.^1,2 She displays no cognitive deficits or psychological disorders (e.g., mental retardation, schizophrenia) that are commonly associated with pica.^3-6 Pregnancy, which is also common in pica, did exist in this patient and may provide some physiologic or psychological insight into the patient’s disorder.⁷ The patient’s bulimia nervosa, however, gives an unusual twist to this case.

In the 18th century, pica was classified together with bulimia simply as an erroneous or aberrant appetite (Box 1).⁸ Pica has been known to occur with—and can be a symptom of—bulimia and anorexia, but it is rarely cited.^8,10 As in other eating disorders, affected individuals are ashamed of their weight, body shape, and body image.¹³

Box 1

Comorbid bulimia and pica disorders tend to work together to accomplish a similar task: weight loss/control. Eating non-nutritive substances occupies space in the stomach, creating a sense of satiety without taking in calories. Therefore, this behavior acts as a substitute for binging in the patient with bulimia.¹⁴

One study identified eight themes associated with pica during pregnancy: keeping practices secret, singularity of the experience, extravagant means for obtaining the craved substance, fears for the effects on the fetus, yielding or not yielding to the cravings, use of the substances as medication, pica and lack of food intake, and sensory experiences other than taste.² All eight of these themes were present in Ms. A.

Evaluation: Needing more and more

By her third pregnancy, Ms. A’s obsession with powder started to take hold. She found it easier to conceal the purging from her partner, so she began purging more often (twice daily) to offset her cravings for the baby powder. Purging was a last resort for the patient and her only means of off-setting her desire for the powder, which relieved her urge to vomit. She ate baby powder throughout the day, even awaking two to three times at night to ingest a few spoonfuls.

Until she presented to us, Ms. A had followed a daily ritual. At 10:30 a.m., when the local drug store opens, she superficially tested the consistency of a certain brand of powder available on the shelves. She then purchased one case (six 14-ounce containers) of powder, went home and sampled each container, and rated them in quality from 1 to 6, with 1 being the bottle of powder she ate that day. The next morning, regardless of how many cases of powder were piled in her closet, she went to the drug store and repeated the process.

Ms. A felt comfortable eating the talc-based powder in her apartment and her mother’s house. She kept some baby powder in her desk at work, but she regularly took an hour-long lunch break to drive back to her apartment and satisfy her craving. She also carried powder in the car, tasting it while driving.

When asked how the powder made her feel, Ms. A replied: “Powder is like nothing else. It makes me feel content and at ease.” Whenever she was irritated, or if the children were frustrating her, she would take a spoonful of powder.

In the beginning, she consumed approximately one 14-ounce bottle per month. When she presented 28 weeks pregnant with her third child, she could not imagine life without baby powder. A spoonful satisfied her for only 5 to 10 minutes before she would desire more. No other substance quelled the cravings. She had tried edible substitutes such as confectioners sugar, cornstarch, and ice chips, but nothing offered the satisfaction she got from powder.

When she is unable to ingest powder, she develops a headache, begins to sweat, gets extremely anxious and irritable, cries profusely, and becomes depressed. If she is abstinent more than 2 days she is unable to sleep and becomes preoccupied with the powder. If powder is not available, she binges and induces vomiting to stifle her craving.

In the hospital she craved powder 2 days after it was removed from her access. She became extremely anxious and distressed. She then ordered as much food as possible so she could purge and forget about the powder.

How would you explain the patient’s psychopathological attraction to baby powder?

Commentary

Patients with pica typically express satisfaction from consuming non-nutrient substances (Box 2). Ms. A’s motive for eating the powder stemmed from what she perceived as its soothing properties.

Other reported cases have alluded to the sensation generated by the texture of soil or chalk in the mouth. Some of these patients also described the importance of the soil’s taste—i.e., particle size—as being second to its texture.¹² The desire to experience a certain texture, color, odor, and taste are important components in pica cravings.¹⁰

Box 2

Pica appears to meet the individual’s need for mental relaxation and sensory pleasure¹⁵ in much the same way that alcohol or drug abusers satisfy their intense desire for euphoria and relaxation. Scientists theorize that alcohol and drug abuse may be exacerbated by or result from a neurochemical imbalance. A similar hypothesis may explain this “variant” in pica patients.

Pregnant women often develop taste aversions for items that are potentially harmful to the developing fetus, such as alcohol and coffee. Expectant mothers may develop utter disgust and provocation of nausea toward items they enjoyed while not gravid. Aversions to foods and other items during pregnancy might be the consequence of homeostatic factors that have evolved as general feto-protective mechanisms.^16,17 The metabolic changes that accompany the gravid state might alter olfactory and taste sensitivity.¹⁷

If a pregnancy-related change in chemical balance can cause taste aversion, certainly a similar situation could evolve into pica. In laboratory rats, intraventricular injection of exogenous neuropeptide Y, a hormone with documented CNS activity, caused taste aversions and elicited geophagia.¹⁸

Ms. A’s ingestion of baby powder itself did not harm the fetus. Stephen Emery, MD, director of perinatal ultrasound at the Cleveland Clinic, notes that talc is inert and the powder’s perfumes probably are benign. He adds, however, that because the powder often has replaced real food, Ms. A placed her unborn child at risk via malnourishment.

Further evaluation: A ‘pleasant’ appearance

Ms. A’s medical history revealed chronic asthma since childhood and gastroesophageal reflux disease. According to her social history, she is dating the father of her expectant child. She has been smoking one pack of cigarettes per day for 2 years but says she does not drink alcohol and has never abused illicit drugs.

Her lab values were as follows (with normal ranges in parentheses): blood urea, 4 mg/dl (9-23); serum iron, 69 mg/dl (42-135); calcium 8.7 mg/dl (8.5-10.5); magnesium, 1.6 mg/dl (1.8-2.4); phosphate, 2.4 mg/dl (2.7-4.6); hemoglobin, 10.0 g/dl (12.0-14.0); hematocrit, 31.1% (37.0-47.0); mean corpuscular volume, 86.4 fl (81-99).

Ms. A appeared well-nourished, appropriately dressed, and well-groomed during our examination. She was alert, oriented and cooperative, and held a pleasant conversation with good eye contact. Her mood was depressed and anxious, and her affect was congruent. Speech was normal in rate, tone, and volume. Her thoughts were well organized and goal-directed. She denied suicidal ideation but had thoughts of harming her fetus. She denied any perceptual disturbances. No intellectual impairment was evident, and her insight and judgment were preserved.

What is the psychiatric diagnosis for this patient? Also, in your view, how likely is she to harm her fetus or her two children? How would you assess and manage that risk?

Commentary

The physiologic cause of pica may be metabolic disturbances in iron, zinc, calcium, potassium, lead, and magnesium.^10,19-22 Ice pica typically is associated with iron deficiency and low hemoglobin levels,^14,20,23,24 although other forms of pica have been linked to iron deficiency.^12,25 Some studies show iron deficiency in nearly half of patients who display ice pica;^20,26 correcting the iron deficiency relieves the cravings for the desired substances.^7,14 Scientists are split as to whether pica results in the deficiency of certain minerals or whether mineral deficiencies cause pica. Mineral deficiencies may alter appetite-regulating brain enzymes that can lead to these cravings.^7,10,11,23

Ms. A’s laboratory values demonstrated decreased hemoglobin, hematocrit, and magnesium levels. Magnesium replacement did not change her eating behavior. Her mild anemia may simply have been an effect of pregnancy.

Treatment: Confronting comorbid depression

Ms. A’s diagnosis was pica, bulimia nervosa-purging type, with comorbid depressive disorder NOS.

She was placed on the selective serotonin reuptake inhibitor sertraline, 12.5 mg/d. The dosage was increased gradually to 50 mg qd. Supportive psychotherapy was provided during the patient’s hospital course.

After her discharge, cognitive therapy was initiated. Ms. A was asked to keep a journal utilizing the “triple column technique,” through which she described a situation in one column, explained the symptoms or unwanted behaviors and emotions evoked by that situation in the second, and wrote down her thoughts in the third.

Ms. A was monitored for signs and symptoms of postpartum depression. After this careful assessment, in which two psychiatrists and the ob/gyn team participated, we concluded that the patient’s transient thoughts of harming her fetus had fully resolved.

Ms. A was educated about nutrition and healthy exercise, as well as birth control options. We also asked to see her as an outpatient.

In the ensuing months, Ms. A reported moderate depressive symptoms but described a significant decrease in her craving for, and consumption of, powder. She continued follow-up treatment with her physician at the women’s care center. Ms. A decided to stop taking sertraline after 2 months because she felt it was not helping her depression and was causing fatigue.

When we followed up after 6 months, Ms. A reported that she and her baby were doing well. She told us that her powder cravings had decreased markedly.

Related resources

• Alliance for Eating Disorders Awareness. www.eatingdisorderinfo.org
• Stein DJ, Bouwer C, van Heerden B. Pica and the obsessive spectrum disorders. S Afr Med J 1996; 86(12 suppl):1586-8, 1591-2.

Drug brand names

• Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article.

History: Learning to worry

Mr. A, 54, is a hotel manager who has struggled with anxiety since childhood. At that time, he suffered primarily from incessant worries. Even then, he knew that his concerns were irrational, but he could not suppress them. Mild illness stirred up thoughts of his own death and then even the possibility of his parents’ death. Water coming from a tap evoked images of disasters from a future global water shortage.

In the classroom, his elaborate concerns about his teachers’ evaluations of him paralyzed him emotionally. While trying to manage this inner turmoil, even his obvious intelligence could not compensate for his time off-task in school, and a subsequent decline in his grades brought about the scrutiny he had dreaded, further exacerbating his anxiety.

By his teenage years, Mr. A developed classic compulsions, such as checking locks and engaging in counting rituals. In his 20s, he also found himself repeatedly returning home to confirm that he had turned off appliances. Over time, the doubt intrinsic to these compulsions only grew, and ultimately the associated anxiety became unbearable. Mr. A turned to increased alcohol use and even a brief experiment with heroin.

After self-medication brought no relief, Mr. A finally sought professional treatment at age 26. Although the compulsions caused the greatest burden, they were the most readily treated symptoms. His behavior-based psychotherapy led to full remission of his most overt symptoms. This treatment also helped alleviate some of his more circumscribed obsessions, but the diffuse worry proved to be more intractable.

After psychotherapy, just as in his childhood, Mr. A still worried about an ever-changing array of subjects. He worried about finances, his own physical health, and his wife’s well being. He worried about his relationship with his customers, as well as his supervisor’s assessment of him. Any physical symptom set off fears that he had cancer. In response to his memory of engaging in low-risk sexual behaviors in his distant past, he struggled to resist thoughts that he had AIDS. He stayed in excellent physical condition, combining strength training with 6 hours of aerobic exercise weekly. Still, he could not escape the nearly constant fear that his death was imminent.

In your view, what single diagnosis best explains Mr. A’s symptoms? What other conditions are you considering—or would you have considered earlier in his life?

Dr. Carter’s observations

The childhood history highlights a major controversy: psychiatric treatment of inattentive children who are not performing well in school. We psychiatrists are accused of sloppy diagnostic overuse of attention-deficit/hyperactivity disorder (ADHD) when “it’s just boys being boys,” and even of conspiracy in overmedicating children with psychostimulants. In my adult psychiatry practice, I more commonly see the consequences of missed cases of ADHD, rather than overdiagnosis, when, after successful treatment in adulthood, “underachieving” men struggle with a new view of their childhood “failures.”

The current case illustrates the need for careful evaluation of inattention. As an adult, Mr. A articulates his anxiety, but as a child, physically active yet silently worried, it would have been easy for an observer to misunderstand the source of his inattention.

The history in his adolescence and early adulthood emphasizes anxiety symptoms. With morbid themes, we must consider the possibility that the anxiety is a component of depression. Pervasive somatic concerns in particular can indicate major depression with psychotic features, a frequently missed diagnosis.

While Mr. A expresses concerns about AIDS and cancer—common themes in delusional depression—his core pathology is excessive worry, the essential feature of generalized anxiety disorder (GAD). Previously, Mr. A met criteria for obsessive-compulsive disorder. His concerns about scrutiny of his behavior also raise suspicion of social anxiety disorder. The complete differential diagnosis would include somatoform disorders, and we should note the comorbid substance abuse history.

So how many diagnoses does Mr. A have?

The disparate symptoms listed in the criteria for GAD cause some to doubt its validity as a true diagnostic entity. The overlap between the criteria for major depression and GAD (Box 1) raises other legitimate concerns.

But when we focus on pathologic worry as the defining feature of this disorder and recognize the associated emotional and physical symptoms, I think the diagnosis of GAD captures the essence of Mr. A’s presentation. Yes, he met criteria for OCD, and he has features of other disorders, but his current anxiety and physical symptoms are best explained by a unifying diagnosis of GAD.

Box 1

Treatment: First try at pharmacologic treatment

When Mr. A’s worries reached the toxic level of fear of imminent death, he sought a psychiatrist’s help. Previous pharmacologic treatment had been limited to brief trials of low dosages of benzodiazepines, typically after emergency room evaluations of some somatic symptom. The benzodiazepines resulted in only minimal improvement and significant daytime sedation. At age 44, at his first appointment with a psychiatrist, Mr. A described not only severe anxiety but also a wide range of physical symptoms. These included tension, dizziness, tingling sensations, migrating pains, disrupted sleep, and low energy.

Mr. A had developed considerable insight about the link between his anxiety and these symptoms, not from psychotherapy but indirectly through extensive medical evaluations. Prior evaluations had included countless emergency room visits, multiple head CT scans and MRIs, and a series of ECGs. None of these led to either a diagnosis or a plan for systematic follow-up until Mr. A independently sought psychiatric treatment.

The psychiatrist prescribed buspirone, titrated up to 10 mg tid, which resulted in minimal improvement of Mr. A’s myriad symptoms. But side effects—including generally disrupted sleep and “crazy dreams”—by far offset any gains, and Mr. A in fact developed symptoms diagnostic of major depression. Over the next several weeks, buspirone was discontinued.

In your view, would you now treat Mr. A for depression? If so, with which agent and for how long?

Dr. Carter’s observations

The salient part of the initial treatment history is the setting. Typical of GAD and panic disorder, much of the early evaluation is done in nonpsychiatric settings. Many patients with anxiety disorders receive no consistent health care. With peak anxiety symptoms manifesting as frightening physical symptoms, such patients present to the emergency room to physicians who are unfamiliar with their longitudinal course. Catastrophic illness is “ruled out,” and with the acute anxiety resolved, no fundamental diagnosis is reached.

With Mr. A’s medical evaluations, we see a typical example: multiple emergency room visits, repeated brain imaging, and emergency ECGs in a man who exercises vigorously without cardiovascular symptoms. The indirect costs to the patient and to society are staggering, with panic disorder and GAD each ranking above lung problems, hypertension, asthma, and back problems in causing lost productivity at work.¹

Mr. A is typical of anxiety disorder patients who do not pursue psychiatric treatment initially. Only one-fourth seek treatment,² and several variables at the outset of his illness predict an even lower rate for patients such as Mr. A. He is male, had an early onset of illness, and did not have a prominent, comorbid mood disorder. His severe symptoms also predict poor compliance once treatment is initiated.³

Understandably, treatment for anxiety disorders often starts with anxiolytics. The common use of benzodiazepines to treat GAD may account for some early studies showing lower sustained remission with GAD compared with other anxiety disorders. Without treating the whole syndrome, sustained response was impossible. In contast, when patients do receive antidepressant medication and stay on it, the literature offers encouragement to those with even severe symptoms: although they do not fare as well as their healthier counterparts early on, patients with severe GAD catch up around the 3-month mark.⁴

Further treatment: The move to antidepressants

Mr. A was next started on sertraline, titrated up to 50 mg/d. At this dosage, he complained of significant sexual side effects and early morning awakening that did not respond to trazodone. Sertraline was stopped and the sexual side effects resolved. He began taking nortriptyline titrated up to 75 mg/d without side effects. He reported considerable improvement, with diminished anxiety, resolution of depressed mood, and less dizziness. As Mr. A stated, he was “not such a hypochondriac anymore.” Some somatic symptoms persisted, and nortriptyline was increased to 100 mg/d, resulting in further improvement (at a nortriptyline level of 114 ug/L).

After 1 month of being nearly symptom-free, Mr. A experienced a recurrence of his anxiety and an associated increase in depression symptoms, which responded to an increase in nortriptyline to 125 mg/d.

His characteristic health concerns persisted, however. Mr. A was unable to contain his worries about having Huntington’s chorea, based on a tremor that he had noted. This particular worry vanished after consultation with a Huntington’s disease expert, but from day to day he relied on his wife for constant reassurance about his physical health. Various treatment interventions were discussed, and Mr. A agreed to increase his nortriptyline further. He never did so, however, as the recurrence of his anxiety symptoms proved to be transient.

In fact, his overall improvement was dramatic. He was able to joke about his previous “hypochondriasis,” and when thoughts about health concerns entered his mind, he was able to quickly dismiss them and reassure himself. At the outset of treatment, it had not been unusual for Mr. A to make several phone calls daily to his psychiatrist seeking reassurance about his general health. During such calls, anything shy of 100% certainty would exacerbate his anxiety. Definitive reassurance would comfort him for anywhere from 1 hour to 3 days. In contrast, on nortriptyline 125 mg/d, Mr. A felt well and would go several months between appointments. His contact with his psychiatrist during those intervals was limited to phone calls to request prescription refills. His phone messages frequently included jokes about whether the psychiatrist was lonely without the frequent phone contact.

How do your patients with complaints of anxiety respond if you suggest treating them with antidepressants? How do you reassure them so they stay the course?

Dr. Carter’s observations

Educational messages and compliance strategies can have a positive impact.⁵ A little time invested in patient education early on can reap big rewards by reducing frantic telephone calls about side effects and the risk of a demoralized patient who discontinues medication prematurely.

For patients who feel every peristaltic wave, knowing that nausea from the initiation of a medication is likely to be gone by the end of the first week of treatment can be pivotal. Such differences are critical in achieving medication trials of adequate duration, which is particularly relevant in GAD.⁶ This finding may account for Mr. A’s variable early response and more robust subsequent response to nortriptyline.

The importance of educational messages is also relevant to patients’ reactions to use of antidepressants to treat their anxiety. This is not a trivial, semantic point. Patients who at first did not even perceive a need for treatment finally recognize that they have anxiety, and you are going to prescribe an antidepressant? Without a lucid explanation, be prepared for an indignant patient who thinks you are ignoring his or her stated concern. Especially with patients accustomed to the immediate effect of diazepam in acute treatment, the expected time course with antidepressants is a critical lesson.

Regarding specific medications, Mr. A’s history again illustrates a typical scenario: benzodiazepines for acute symptoms and buspirone when he eventually presented to a psychiatrist. With typical comorbidity, however, the use of broader-spectrum antidepressants—selective serotonin reuptake inhibitors or serotonin/norepinephrine reuptake inhibitors—represents a more logical first-line choice. Head-to-head trials between venlafaxine XR and buspirone further support this position.⁷ With the emergence of sexual side effects with sertraline in this particular case, the switch to a different category of antidepressant is sensible.

I support the use in GAD of antidepressant dosages comparable to those used to treat major depression. I can recall discussions about how anxiety disorder patients cannot tolerate full doses of antidepressants and do not need them anyway, but dosage response studies and clinical experience would argue otherwise. Compliance is a crucial factor with anxiety patients, and nothing fosters compliance like robust clinical response. In treatment of GAD, the data are clear: Use antidepressants at full dosages.

Complications: hypochondriacs get ill, too

Mr. A remained well for 8 months, but then became more concerned about an increase in his resting heart rate to 90 bpm, some heartburn, and a slight decrease in his libido.

At Mr. A’s request, liver function tests (LFTs) and an ECG were obtained. The latter was normal, but his LFT scores remained elevated (ALT=121, AST=73) without significant change from premedication results (130, 64, respectively).

Three months later, Mr. A continued to report that he was feeling well, but he now noted distress related to long-term memory deficits that had emerged, in retrospect, relatively early in this nortriptyline trial. His dosage was decreased to 100 mg/d.

At a routine physical examination the next month, Mr. A’s internist noted the persistence of elevated LFT scores. The internist had been advised of Mr. A’s anxiety-ridden response to any discussion of possible medical illness and agreed to simply recommend that Mr. A discontinue his vitamin A and D supplements with periodic administration of LFTs.

A year later, however, with advancing knowledge about chronic hepatitis, the internist found that Mr. A did indeed have hepatitis C. Mr. A handled this news relatively well initially, but 4 months later his defenses began to break down. His previously lighthearted humor assumed more morbid tones, as he attempted to joke about how he would probably die from liver cancer while he worried about a hangnail. He became dependent on his wife’s reassurance again and required her presence during appointments so that she could retain information from those meetings and later use it to reassure him.

The role of his moderate alcohol intake came under more scrutiny, and his psychiatrist advised Mr. A to stop drinking altogether. Transient episodes of severe anxiety were treated with low doses of lorazepam over several weeks. Mr. A began to obsess about the timing of any further work-up regarding his hepatitis C, including the question of a liver biopsy. He wanted to make sure that he did not get any LFTs prior to travel, knowing that he would obsess about the results and ruin the vacation for his wife and himself.

Several months later, after more than 3 years on nortriptyline, it became clear that Mr. A’s anxiety about his hepatitis—combined with his ongoing concern about memory side effects—indicated a need to change his medication. A taper of nortriptyline resulted in significantly increased anxiety symptoms, but also in an obvious improvement in his memory.

In your view, what would be your next choice of therapy? Another antidepressant? Back to an anxiolytic? Why?

Dr. Carter’s observations

The general goal is to maintain long-term compliance with treatment of a chronic condition. Therefore, judicious use of benzodiazepines as adjunctive treatment might play a crucial role during flare-ups of the illness, as when Mr. A learns that he actually has a serious medical condition other than his anxiety disorder. We have already established that anxiolytics are not a sensible choice as the foundation of treatment, but they can help patients who experience temporary increases in anxiety with initiation of antidepressant treatment.

We have already reviewed the critical nature of education in treatment, as anxiety limits one’s ability to process new information. Mr. A’s idea of bringing his wife to appointments is a simple and elegant means of his later testing any possible distortions of the conversation. I have patients who audiotape sessions for their subsequent use, and anxious patients frequently attribute significant value to the chance to review certain points “on their own turf” and when their anxiety level is optimally reduced for learning.

In the case of Mr. A, there was a sound working relationship between the internist and the psychiatrist, which is an asset in managing somatic presentations of anxiety disorders, particularly with the risk of depression and even suicide associated with potential interferon treatment of hepatitis.

Final chapter: Confronting anxiety, side effects

Fluoxetine was the next form of treatment, subsequently titrated up to 60 mg/d. Mr. A’s worries about the state of his liver improved, but he was still troubled by infrequent, brief episodes when his anxiety would soar. The overlap between nonspecific symptoms of progressive liver disease—nausea, fatigue, and abdominal pains—and Mr. A’s baseline anxiety symptoms presented new fodder for his anxiety.

His response to fluoxetine illustrated a clear dose-response relationship: His anxiety improved after each dosage increase, and symptoms escalated whenever the dosage was decreased to address a given side effect. Mr. A reported tolerable sexual side effects but ultimately nightmares were too distressing, limiting the quality of his nighttime sleep and resulting in daytime fatigue.

To address this sleep disruption and sexual side effects, fluoxetine was discontinued and Mr. A began taking nefazodone. He took up to 375 mg/d for approximately 20 months with moderate benefit, offset only somewhat by a recurrence of vivid dreams. Then case reports appeared possibly linking liver failure to nefazodone. Mr. A agreed to stop this agent and to evaluate gabapentin as an anxiolytic.

With limited dosages of gabapentin, up to a total of 1,200 mg/d, Mr. A noted significantly improved anxiety symptoms overall, but nightmares and other vivid dreams still interfered with his recovery.

No clear correlation between medication or anxiety level and severity of sleep disturbance emerged. The nature of Mr. A’s work rendered the “sleep hygiene” intervention of a regular sleep cycle impossible, and he understandably did not consider a career shift feasible. A sleep disorders consultation to address this one remaining symptom is under way.

Overall, Mr. A is delighted with his progress. He is now able to participate in informed decision making about treatment of his hepatitis, rather than merely obsess about obtaining LFTs.

Related resources

• Anxiety Disorders Association of America. www.adaa.org. Information for psychiatrists, researchers, residents, patients, caregivers, and the media
• About.com: Generalized Anxiety Disorder: A Real Illness. http://www.MentalHealth.About.com/library/mh/anx/blgadri1.htm
• National Institute of Mental Health: Anxiety Disorders http://www.nimh.nih.gov/anxiety/anxietymenu.cfm

Drug brand names

• Buspirone • Buspar
• Diazepam • Valium
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Lorazepam • Ativan
• Nefazodone • Serzone
• Nortriptyline • Pamelor
• Sertraline • Zoloft
• Trazodone • Desyrel
• Venlafaxine • Effexor

Disclosure

The author reports that he received research support from Eli Lilly and Co. and Pfizer Inc., and serves as a consultant for Eli Lilly and Co. and Ortho-McNeil Pharmaceutical.

History: Learning to worry

Mr. A, 54, is a hotel manager who has struggled with anxiety since childhood. At that time, he suffered primarily from incessant worries. Even then, he knew that his concerns were irrational, but he could not suppress them. Mild illness stirred up thoughts of his own death and then even the possibility of his parents’ death. Water coming from a tap evoked images of disasters from a future global water shortage.

In the classroom, his elaborate concerns about his teachers’ evaluations of him paralyzed him emotionally. While trying to manage this inner turmoil, even his obvious intelligence could not compensate for his time off-task in school, and a subsequent decline in his grades brought about the scrutiny he had dreaded, further exacerbating his anxiety.

By his teenage years, Mr. A developed classic compulsions, such as checking locks and engaging in counting rituals. In his 20s, he also found himself repeatedly returning home to confirm that he had turned off appliances. Over time, the doubt intrinsic to these compulsions only grew, and ultimately the associated anxiety became unbearable. Mr. A turned to increased alcohol use and even a brief experiment with heroin.

After self-medication brought no relief, Mr. A finally sought professional treatment at age 26. Although the compulsions caused the greatest burden, they were the most readily treated symptoms. His behavior-based psychotherapy led to full remission of his most overt symptoms. This treatment also helped alleviate some of his more circumscribed obsessions, but the diffuse worry proved to be more intractable.

After psychotherapy, just as in his childhood, Mr. A still worried about an ever-changing array of subjects. He worried about finances, his own physical health, and his wife’s well being. He worried about his relationship with his customers, as well as his supervisor’s assessment of him. Any physical symptom set off fears that he had cancer. In response to his memory of engaging in low-risk sexual behaviors in his distant past, he struggled to resist thoughts that he had AIDS. He stayed in excellent physical condition, combining strength training with 6 hours of aerobic exercise weekly. Still, he could not escape the nearly constant fear that his death was imminent.

In your view, what single diagnosis best explains Mr. A’s symptoms? What other conditions are you considering—or would you have considered earlier in his life?

Dr. Carter’s observations

The childhood history highlights a major controversy: psychiatric treatment of inattentive children who are not performing well in school. We psychiatrists are accused of sloppy diagnostic overuse of attention-deficit/hyperactivity disorder (ADHD) when “it’s just boys being boys,” and even of conspiracy in overmedicating children with psychostimulants. In my adult psychiatry practice, I more commonly see the consequences of missed cases of ADHD, rather than overdiagnosis, when, after successful treatment in adulthood, “underachieving” men struggle with a new view of their childhood “failures.”

The current case illustrates the need for careful evaluation of inattention. As an adult, Mr. A articulates his anxiety, but as a child, physically active yet silently worried, it would have been easy for an observer to misunderstand the source of his inattention.

The history in his adolescence and early adulthood emphasizes anxiety symptoms. With morbid themes, we must consider the possibility that the anxiety is a component of depression. Pervasive somatic concerns in particular can indicate major depression with psychotic features, a frequently missed diagnosis.

While Mr. A expresses concerns about AIDS and cancer—common themes in delusional depression—his core pathology is excessive worry, the essential feature of generalized anxiety disorder (GAD). Previously, Mr. A met criteria for obsessive-compulsive disorder. His concerns about scrutiny of his behavior also raise suspicion of social anxiety disorder. The complete differential diagnosis would include somatoform disorders, and we should note the comorbid substance abuse history.

So how many diagnoses does Mr. A have?

The disparate symptoms listed in the criteria for GAD cause some to doubt its validity as a true diagnostic entity. The overlap between the criteria for major depression and GAD (Box 1) raises other legitimate concerns.

But when we focus on pathologic worry as the defining feature of this disorder and recognize the associated emotional and physical symptoms, I think the diagnosis of GAD captures the essence of Mr. A’s presentation. Yes, he met criteria for OCD, and he has features of other disorders, but his current anxiety and physical symptoms are best explained by a unifying diagnosis of GAD.

Box 1

Treatment: First try at pharmacologic treatment

When Mr. A’s worries reached the toxic level of fear of imminent death, he sought a psychiatrist’s help. Previous pharmacologic treatment had been limited to brief trials of low dosages of benzodiazepines, typically after emergency room evaluations of some somatic symptom. The benzodiazepines resulted in only minimal improvement and significant daytime sedation. At age 44, at his first appointment with a psychiatrist, Mr. A described not only severe anxiety but also a wide range of physical symptoms. These included tension, dizziness, tingling sensations, migrating pains, disrupted sleep, and low energy.

Mr. A had developed considerable insight about the link between his anxiety and these symptoms, not from psychotherapy but indirectly through extensive medical evaluations. Prior evaluations had included countless emergency room visits, multiple head CT scans and MRIs, and a series of ECGs. None of these led to either a diagnosis or a plan for systematic follow-up until Mr. A independently sought psychiatric treatment.

The psychiatrist prescribed buspirone, titrated up to 10 mg tid, which resulted in minimal improvement of Mr. A’s myriad symptoms. But side effects—including generally disrupted sleep and “crazy dreams”—by far offset any gains, and Mr. A in fact developed symptoms diagnostic of major depression. Over the next several weeks, buspirone was discontinued.

In your view, would you now treat Mr. A for depression? If so, with which agent and for how long?

Dr. Carter’s observations

The salient part of the initial treatment history is the setting. Typical of GAD and panic disorder, much of the early evaluation is done in nonpsychiatric settings. Many patients with anxiety disorders receive no consistent health care. With peak anxiety symptoms manifesting as frightening physical symptoms, such patients present to the emergency room to physicians who are unfamiliar with their longitudinal course. Catastrophic illness is “ruled out,” and with the acute anxiety resolved, no fundamental diagnosis is reached.

With Mr. A’s medical evaluations, we see a typical example: multiple emergency room visits, repeated brain imaging, and emergency ECGs in a man who exercises vigorously without cardiovascular symptoms. The indirect costs to the patient and to society are staggering, with panic disorder and GAD each ranking above lung problems, hypertension, asthma, and back problems in causing lost productivity at work.¹

Mr. A is typical of anxiety disorder patients who do not pursue psychiatric treatment initially. Only one-fourth seek treatment,² and several variables at the outset of his illness predict an even lower rate for patients such as Mr. A. He is male, had an early onset of illness, and did not have a prominent, comorbid mood disorder. His severe symptoms also predict poor compliance once treatment is initiated.³

Understandably, treatment for anxiety disorders often starts with anxiolytics. The common use of benzodiazepines to treat GAD may account for some early studies showing lower sustained remission with GAD compared with other anxiety disorders. Without treating the whole syndrome, sustained response was impossible. In contast, when patients do receive antidepressant medication and stay on it, the literature offers encouragement to those with even severe symptoms: although they do not fare as well as their healthier counterparts early on, patients with severe GAD catch up around the 3-month mark.⁴

Further treatment: The move to antidepressants

Mr. A was next started on sertraline, titrated up to 50 mg/d. At this dosage, he complained of significant sexual side effects and early morning awakening that did not respond to trazodone. Sertraline was stopped and the sexual side effects resolved. He began taking nortriptyline titrated up to 75 mg/d without side effects. He reported considerable improvement, with diminished anxiety, resolution of depressed mood, and less dizziness. As Mr. A stated, he was “not such a hypochondriac anymore.” Some somatic symptoms persisted, and nortriptyline was increased to 100 mg/d, resulting in further improvement (at a nortriptyline level of 114 ug/L).

After 1 month of being nearly symptom-free, Mr. A experienced a recurrence of his anxiety and an associated increase in depression symptoms, which responded to an increase in nortriptyline to 125 mg/d.

His characteristic health concerns persisted, however. Mr. A was unable to contain his worries about having Huntington’s chorea, based on a tremor that he had noted. This particular worry vanished after consultation with a Huntington’s disease expert, but from day to day he relied on his wife for constant reassurance about his physical health. Various treatment interventions were discussed, and Mr. A agreed to increase his nortriptyline further. He never did so, however, as the recurrence of his anxiety symptoms proved to be transient.

In fact, his overall improvement was dramatic. He was able to joke about his previous “hypochondriasis,” and when thoughts about health concerns entered his mind, he was able to quickly dismiss them and reassure himself. At the outset of treatment, it had not been unusual for Mr. A to make several phone calls daily to his psychiatrist seeking reassurance about his general health. During such calls, anything shy of 100% certainty would exacerbate his anxiety. Definitive reassurance would comfort him for anywhere from 1 hour to 3 days. In contrast, on nortriptyline 125 mg/d, Mr. A felt well and would go several months between appointments. His contact with his psychiatrist during those intervals was limited to phone calls to request prescription refills. His phone messages frequently included jokes about whether the psychiatrist was lonely without the frequent phone contact.

How do your patients with complaints of anxiety respond if you suggest treating them with antidepressants? How do you reassure them so they stay the course?

Dr. Carter’s observations

Educational messages and compliance strategies can have a positive impact.⁵ A little time invested in patient education early on can reap big rewards by reducing frantic telephone calls about side effects and the risk of a demoralized patient who discontinues medication prematurely.

For patients who feel every peristaltic wave, knowing that nausea from the initiation of a medication is likely to be gone by the end of the first week of treatment can be pivotal. Such differences are critical in achieving medication trials of adequate duration, which is particularly relevant in GAD.⁶ This finding may account for Mr. A’s variable early response and more robust subsequent response to nortriptyline.

The importance of educational messages is also relevant to patients’ reactions to use of antidepressants to treat their anxiety. This is not a trivial, semantic point. Patients who at first did not even perceive a need for treatment finally recognize that they have anxiety, and you are going to prescribe an antidepressant? Without a lucid explanation, be prepared for an indignant patient who thinks you are ignoring his or her stated concern. Especially with patients accustomed to the immediate effect of diazepam in acute treatment, the expected time course with antidepressants is a critical lesson.

Regarding specific medications, Mr. A’s history again illustrates a typical scenario: benzodiazepines for acute symptoms and buspirone when he eventually presented to a psychiatrist. With typical comorbidity, however, the use of broader-spectrum antidepressants—selective serotonin reuptake inhibitors or serotonin/norepinephrine reuptake inhibitors—represents a more logical first-line choice. Head-to-head trials between venlafaxine XR and buspirone further support this position.⁷ With the emergence of sexual side effects with sertraline in this particular case, the switch to a different category of antidepressant is sensible.

I support the use in GAD of antidepressant dosages comparable to those used to treat major depression. I can recall discussions about how anxiety disorder patients cannot tolerate full doses of antidepressants and do not need them anyway, but dosage response studies and clinical experience would argue otherwise. Compliance is a crucial factor with anxiety patients, and nothing fosters compliance like robust clinical response. In treatment of GAD, the data are clear: Use antidepressants at full dosages.

Complications: hypochondriacs get ill, too

Mr. A remained well for 8 months, but then became more concerned about an increase in his resting heart rate to 90 bpm, some heartburn, and a slight decrease in his libido.

At Mr. A’s request, liver function tests (LFTs) and an ECG were obtained. The latter was normal, but his LFT scores remained elevated (ALT=121, AST=73) without significant change from premedication results (130, 64, respectively).

Three months later, Mr. A continued to report that he was feeling well, but he now noted distress related to long-term memory deficits that had emerged, in retrospect, relatively early in this nortriptyline trial. His dosage was decreased to 100 mg/d.

At a routine physical examination the next month, Mr. A’s internist noted the persistence of elevated LFT scores. The internist had been advised of Mr. A’s anxiety-ridden response to any discussion of possible medical illness and agreed to simply recommend that Mr. A discontinue his vitamin A and D supplements with periodic administration of LFTs.

A year later, however, with advancing knowledge about chronic hepatitis, the internist found that Mr. A did indeed have hepatitis C. Mr. A handled this news relatively well initially, but 4 months later his defenses began to break down. His previously lighthearted humor assumed more morbid tones, as he attempted to joke about how he would probably die from liver cancer while he worried about a hangnail. He became dependent on his wife’s reassurance again and required her presence during appointments so that she could retain information from those meetings and later use it to reassure him.

The role of his moderate alcohol intake came under more scrutiny, and his psychiatrist advised Mr. A to stop drinking altogether. Transient episodes of severe anxiety were treated with low doses of lorazepam over several weeks. Mr. A began to obsess about the timing of any further work-up regarding his hepatitis C, including the question of a liver biopsy. He wanted to make sure that he did not get any LFTs prior to travel, knowing that he would obsess about the results and ruin the vacation for his wife and himself.

Several months later, after more than 3 years on nortriptyline, it became clear that Mr. A’s anxiety about his hepatitis—combined with his ongoing concern about memory side effects—indicated a need to change his medication. A taper of nortriptyline resulted in significantly increased anxiety symptoms, but also in an obvious improvement in his memory.

In your view, what would be your next choice of therapy? Another antidepressant? Back to an anxiolytic? Why?

Dr. Carter’s observations

The general goal is to maintain long-term compliance with treatment of a chronic condition. Therefore, judicious use of benzodiazepines as adjunctive treatment might play a crucial role during flare-ups of the illness, as when Mr. A learns that he actually has a serious medical condition other than his anxiety disorder. We have already established that anxiolytics are not a sensible choice as the foundation of treatment, but they can help patients who experience temporary increases in anxiety with initiation of antidepressant treatment.

We have already reviewed the critical nature of education in treatment, as anxiety limits one’s ability to process new information. Mr. A’s idea of bringing his wife to appointments is a simple and elegant means of his later testing any possible distortions of the conversation. I have patients who audiotape sessions for their subsequent use, and anxious patients frequently attribute significant value to the chance to review certain points “on their own turf” and when their anxiety level is optimally reduced for learning.

In the case of Mr. A, there was a sound working relationship between the internist and the psychiatrist, which is an asset in managing somatic presentations of anxiety disorders, particularly with the risk of depression and even suicide associated with potential interferon treatment of hepatitis.

Final chapter: Confronting anxiety, side effects

Fluoxetine was the next form of treatment, subsequently titrated up to 60 mg/d. Mr. A’s worries about the state of his liver improved, but he was still troubled by infrequent, brief episodes when his anxiety would soar. The overlap between nonspecific symptoms of progressive liver disease—nausea, fatigue, and abdominal pains—and Mr. A’s baseline anxiety symptoms presented new fodder for his anxiety.

His response to fluoxetine illustrated a clear dose-response relationship: His anxiety improved after each dosage increase, and symptoms escalated whenever the dosage was decreased to address a given side effect. Mr. A reported tolerable sexual side effects but ultimately nightmares were too distressing, limiting the quality of his nighttime sleep and resulting in daytime fatigue.

To address this sleep disruption and sexual side effects, fluoxetine was discontinued and Mr. A began taking nefazodone. He took up to 375 mg/d for approximately 20 months with moderate benefit, offset only somewhat by a recurrence of vivid dreams. Then case reports appeared possibly linking liver failure to nefazodone. Mr. A agreed to stop this agent and to evaluate gabapentin as an anxiolytic.

With limited dosages of gabapentin, up to a total of 1,200 mg/d, Mr. A noted significantly improved anxiety symptoms overall, but nightmares and other vivid dreams still interfered with his recovery.

No clear correlation between medication or anxiety level and severity of sleep disturbance emerged. The nature of Mr. A’s work rendered the “sleep hygiene” intervention of a regular sleep cycle impossible, and he understandably did not consider a career shift feasible. A sleep disorders consultation to address this one remaining symptom is under way.

Overall, Mr. A is delighted with his progress. He is now able to participate in informed decision making about treatment of his hepatitis, rather than merely obsess about obtaining LFTs.

Related resources

• Anxiety Disorders Association of America. www.adaa.org. Information for psychiatrists, researchers, residents, patients, caregivers, and the media
• About.com: Generalized Anxiety Disorder: A Real Illness. http://www.MentalHealth.About.com/library/mh/anx/blgadri1.htm
• National Institute of Mental Health: Anxiety Disorders http://www.nimh.nih.gov/anxiety/anxietymenu.cfm

Drug brand names

• Buspirone • Buspar
• Diazepam • Valium
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Lorazepam • Ativan
• Nefazodone • Serzone
• Nortriptyline • Pamelor
• Sertraline • Zoloft
• Trazodone • Desyrel
• Venlafaxine • Effexor

Disclosure

The author reports that he received research support from Eli Lilly and Co. and Pfizer Inc., and serves as a consultant for Eli Lilly and Co. and Ortho-McNeil Pharmaceutical.

History: Learning to worry

Mr. A, 54, is a hotel manager who has struggled with anxiety since childhood. At that time, he suffered primarily from incessant worries. Even then, he knew that his concerns were irrational, but he could not suppress them. Mild illness stirred up thoughts of his own death and then even the possibility of his parents’ death. Water coming from a tap evoked images of disasters from a future global water shortage.

In the classroom, his elaborate concerns about his teachers’ evaluations of him paralyzed him emotionally. While trying to manage this inner turmoil, even his obvious intelligence could not compensate for his time off-task in school, and a subsequent decline in his grades brought about the scrutiny he had dreaded, further exacerbating his anxiety.

By his teenage years, Mr. A developed classic compulsions, such as checking locks and engaging in counting rituals. In his 20s, he also found himself repeatedly returning home to confirm that he had turned off appliances. Over time, the doubt intrinsic to these compulsions only grew, and ultimately the associated anxiety became unbearable. Mr. A turned to increased alcohol use and even a brief experiment with heroin.

After self-medication brought no relief, Mr. A finally sought professional treatment at age 26. Although the compulsions caused the greatest burden, they were the most readily treated symptoms. His behavior-based psychotherapy led to full remission of his most overt symptoms. This treatment also helped alleviate some of his more circumscribed obsessions, but the diffuse worry proved to be more intractable.

After psychotherapy, just as in his childhood, Mr. A still worried about an ever-changing array of subjects. He worried about finances, his own physical health, and his wife’s well being. He worried about his relationship with his customers, as well as his supervisor’s assessment of him. Any physical symptom set off fears that he had cancer. In response to his memory of engaging in low-risk sexual behaviors in his distant past, he struggled to resist thoughts that he had AIDS. He stayed in excellent physical condition, combining strength training with 6 hours of aerobic exercise weekly. Still, he could not escape the nearly constant fear that his death was imminent.

In your view, what single diagnosis best explains Mr. A’s symptoms? What other conditions are you considering—or would you have considered earlier in his life?

Dr. Carter’s observations

The childhood history highlights a major controversy: psychiatric treatment of inattentive children who are not performing well in school. We psychiatrists are accused of sloppy diagnostic overuse of attention-deficit/hyperactivity disorder (ADHD) when “it’s just boys being boys,” and even of conspiracy in overmedicating children with psychostimulants. In my adult psychiatry practice, I more commonly see the consequences of missed cases of ADHD, rather than overdiagnosis, when, after successful treatment in adulthood, “underachieving” men struggle with a new view of their childhood “failures.”

The current case illustrates the need for careful evaluation of inattention. As an adult, Mr. A articulates his anxiety, but as a child, physically active yet silently worried, it would have been easy for an observer to misunderstand the source of his inattention.

The history in his adolescence and early adulthood emphasizes anxiety symptoms. With morbid themes, we must consider the possibility that the anxiety is a component of depression. Pervasive somatic concerns in particular can indicate major depression with psychotic features, a frequently missed diagnosis.

While Mr. A expresses concerns about AIDS and cancer—common themes in delusional depression—his core pathology is excessive worry, the essential feature of generalized anxiety disorder (GAD). Previously, Mr. A met criteria for obsessive-compulsive disorder. His concerns about scrutiny of his behavior also raise suspicion of social anxiety disorder. The complete differential diagnosis would include somatoform disorders, and we should note the comorbid substance abuse history.

So how many diagnoses does Mr. A have?

The disparate symptoms listed in the criteria for GAD cause some to doubt its validity as a true diagnostic entity. The overlap between the criteria for major depression and GAD (Box 1) raises other legitimate concerns.

But when we focus on pathologic worry as the defining feature of this disorder and recognize the associated emotional and physical symptoms, I think the diagnosis of GAD captures the essence of Mr. A’s presentation. Yes, he met criteria for OCD, and he has features of other disorders, but his current anxiety and physical symptoms are best explained by a unifying diagnosis of GAD.

Box 1

Treatment: First try at pharmacologic treatment

When Mr. A’s worries reached the toxic level of fear of imminent death, he sought a psychiatrist’s help. Previous pharmacologic treatment had been limited to brief trials of low dosages of benzodiazepines, typically after emergency room evaluations of some somatic symptom. The benzodiazepines resulted in only minimal improvement and significant daytime sedation. At age 44, at his first appointment with a psychiatrist, Mr. A described not only severe anxiety but also a wide range of physical symptoms. These included tension, dizziness, tingling sensations, migrating pains, disrupted sleep, and low energy.

Mr. A had developed considerable insight about the link between his anxiety and these symptoms, not from psychotherapy but indirectly through extensive medical evaluations. Prior evaluations had included countless emergency room visits, multiple head CT scans and MRIs, and a series of ECGs. None of these led to either a diagnosis or a plan for systematic follow-up until Mr. A independently sought psychiatric treatment.

The psychiatrist prescribed buspirone, titrated up to 10 mg tid, which resulted in minimal improvement of Mr. A’s myriad symptoms. But side effects—including generally disrupted sleep and “crazy dreams”—by far offset any gains, and Mr. A in fact developed symptoms diagnostic of major depression. Over the next several weeks, buspirone was discontinued.

In your view, would you now treat Mr. A for depression? If so, with which agent and for how long?

Dr. Carter’s observations

The salient part of the initial treatment history is the setting. Typical of GAD and panic disorder, much of the early evaluation is done in nonpsychiatric settings. Many patients with anxiety disorders receive no consistent health care. With peak anxiety symptoms manifesting as frightening physical symptoms, such patients present to the emergency room to physicians who are unfamiliar with their longitudinal course. Catastrophic illness is “ruled out,” and with the acute anxiety resolved, no fundamental diagnosis is reached.

With Mr. A’s medical evaluations, we see a typical example: multiple emergency room visits, repeated brain imaging, and emergency ECGs in a man who exercises vigorously without cardiovascular symptoms. The indirect costs to the patient and to society are staggering, with panic disorder and GAD each ranking above lung problems, hypertension, asthma, and back problems in causing lost productivity at work.¹

Mr. A is typical of anxiety disorder patients who do not pursue psychiatric treatment initially. Only one-fourth seek treatment,² and several variables at the outset of his illness predict an even lower rate for patients such as Mr. A. He is male, had an early onset of illness, and did not have a prominent, comorbid mood disorder. His severe symptoms also predict poor compliance once treatment is initiated.³

Understandably, treatment for anxiety disorders often starts with anxiolytics. The common use of benzodiazepines to treat GAD may account for some early studies showing lower sustained remission with GAD compared with other anxiety disorders. Without treating the whole syndrome, sustained response was impossible. In contast, when patients do receive antidepressant medication and stay on it, the literature offers encouragement to those with even severe symptoms: although they do not fare as well as their healthier counterparts early on, patients with severe GAD catch up around the 3-month mark.⁴

Further treatment: The move to antidepressants

Mr. A was next started on sertraline, titrated up to 50 mg/d. At this dosage, he complained of significant sexual side effects and early morning awakening that did not respond to trazodone. Sertraline was stopped and the sexual side effects resolved. He began taking nortriptyline titrated up to 75 mg/d without side effects. He reported considerable improvement, with diminished anxiety, resolution of depressed mood, and less dizziness. As Mr. A stated, he was “not such a hypochondriac anymore.” Some somatic symptoms persisted, and nortriptyline was increased to 100 mg/d, resulting in further improvement (at a nortriptyline level of 114 ug/L).

After 1 month of being nearly symptom-free, Mr. A experienced a recurrence of his anxiety and an associated increase in depression symptoms, which responded to an increase in nortriptyline to 125 mg/d.

His characteristic health concerns persisted, however. Mr. A was unable to contain his worries about having Huntington’s chorea, based on a tremor that he had noted. This particular worry vanished after consultation with a Huntington’s disease expert, but from day to day he relied on his wife for constant reassurance about his physical health. Various treatment interventions were discussed, and Mr. A agreed to increase his nortriptyline further. He never did so, however, as the recurrence of his anxiety symptoms proved to be transient.

In fact, his overall improvement was dramatic. He was able to joke about his previous “hypochondriasis,” and when thoughts about health concerns entered his mind, he was able to quickly dismiss them and reassure himself. At the outset of treatment, it had not been unusual for Mr. A to make several phone calls daily to his psychiatrist seeking reassurance about his general health. During such calls, anything shy of 100% certainty would exacerbate his anxiety. Definitive reassurance would comfort him for anywhere from 1 hour to 3 days. In contrast, on nortriptyline 125 mg/d, Mr. A felt well and would go several months between appointments. His contact with his psychiatrist during those intervals was limited to phone calls to request prescription refills. His phone messages frequently included jokes about whether the psychiatrist was lonely without the frequent phone contact.

How do your patients with complaints of anxiety respond if you suggest treating them with antidepressants? How do you reassure them so they stay the course?

Dr. Carter’s observations

Educational messages and compliance strategies can have a positive impact.⁵ A little time invested in patient education early on can reap big rewards by reducing frantic telephone calls about side effects and the risk of a demoralized patient who discontinues medication prematurely.

For patients who feel every peristaltic wave, knowing that nausea from the initiation of a medication is likely to be gone by the end of the first week of treatment can be pivotal. Such differences are critical in achieving medication trials of adequate duration, which is particularly relevant in GAD.⁶ This finding may account for Mr. A’s variable early response and more robust subsequent response to nortriptyline.

The importance of educational messages is also relevant to patients’ reactions to use of antidepressants to treat their anxiety. This is not a trivial, semantic point. Patients who at first did not even perceive a need for treatment finally recognize that they have anxiety, and you are going to prescribe an antidepressant? Without a lucid explanation, be prepared for an indignant patient who thinks you are ignoring his or her stated concern. Especially with patients accustomed to the immediate effect of diazepam in acute treatment, the expected time course with antidepressants is a critical lesson.

Regarding specific medications, Mr. A’s history again illustrates a typical scenario: benzodiazepines for acute symptoms and buspirone when he eventually presented to a psychiatrist. With typical comorbidity, however, the use of broader-spectrum antidepressants—selective serotonin reuptake inhibitors or serotonin/norepinephrine reuptake inhibitors—represents a more logical first-line choice. Head-to-head trials between venlafaxine XR and buspirone further support this position.⁷ With the emergence of sexual side effects with sertraline in this particular case, the switch to a different category of antidepressant is sensible.

I support the use in GAD of antidepressant dosages comparable to those used to treat major depression. I can recall discussions about how anxiety disorder patients cannot tolerate full doses of antidepressants and do not need them anyway, but dosage response studies and clinical experience would argue otherwise. Compliance is a crucial factor with anxiety patients, and nothing fosters compliance like robust clinical response. In treatment of GAD, the data are clear: Use antidepressants at full dosages.

Complications: hypochondriacs get ill, too

Mr. A remained well for 8 months, but then became more concerned about an increase in his resting heart rate to 90 bpm, some heartburn, and a slight decrease in his libido.

At Mr. A’s request, liver function tests (LFTs) and an ECG were obtained. The latter was normal, but his LFT scores remained elevated (ALT=121, AST=73) without significant change from premedication results (130, 64, respectively).

Three months later, Mr. A continued to report that he was feeling well, but he now noted distress related to long-term memory deficits that had emerged, in retrospect, relatively early in this nortriptyline trial. His dosage was decreased to 100 mg/d.

At a routine physical examination the next month, Mr. A’s internist noted the persistence of elevated LFT scores. The internist had been advised of Mr. A’s anxiety-ridden response to any discussion of possible medical illness and agreed to simply recommend that Mr. A discontinue his vitamin A and D supplements with periodic administration of LFTs.

A year later, however, with advancing knowledge about chronic hepatitis, the internist found that Mr. A did indeed have hepatitis C. Mr. A handled this news relatively well initially, but 4 months later his defenses began to break down. His previously lighthearted humor assumed more morbid tones, as he attempted to joke about how he would probably die from liver cancer while he worried about a hangnail. He became dependent on his wife’s reassurance again and required her presence during appointments so that she could retain information from those meetings and later use it to reassure him.

The role of his moderate alcohol intake came under more scrutiny, and his psychiatrist advised Mr. A to stop drinking altogether. Transient episodes of severe anxiety were treated with low doses of lorazepam over several weeks. Mr. A began to obsess about the timing of any further work-up regarding his hepatitis C, including the question of a liver biopsy. He wanted to make sure that he did not get any LFTs prior to travel, knowing that he would obsess about the results and ruin the vacation for his wife and himself.

Several months later, after more than 3 years on nortriptyline, it became clear that Mr. A’s anxiety about his hepatitis—combined with his ongoing concern about memory side effects—indicated a need to change his medication. A taper of nortriptyline resulted in significantly increased anxiety symptoms, but also in an obvious improvement in his memory.

In your view, what would be your next choice of therapy? Another antidepressant? Back to an anxiolytic? Why?

Dr. Carter’s observations

The general goal is to maintain long-term compliance with treatment of a chronic condition. Therefore, judicious use of benzodiazepines as adjunctive treatment might play a crucial role during flare-ups of the illness, as when Mr. A learns that he actually has a serious medical condition other than his anxiety disorder. We have already established that anxiolytics are not a sensible choice as the foundation of treatment, but they can help patients who experience temporary increases in anxiety with initiation of antidepressant treatment.

We have already reviewed the critical nature of education in treatment, as anxiety limits one’s ability to process new information. Mr. A’s idea of bringing his wife to appointments is a simple and elegant means of his later testing any possible distortions of the conversation. I have patients who audiotape sessions for their subsequent use, and anxious patients frequently attribute significant value to the chance to review certain points “on their own turf” and when their anxiety level is optimally reduced for learning.

In the case of Mr. A, there was a sound working relationship between the internist and the psychiatrist, which is an asset in managing somatic presentations of anxiety disorders, particularly with the risk of depression and even suicide associated with potential interferon treatment of hepatitis.

Final chapter: Confronting anxiety, side effects

Fluoxetine was the next form of treatment, subsequently titrated up to 60 mg/d. Mr. A’s worries about the state of his liver improved, but he was still troubled by infrequent, brief episodes when his anxiety would soar. The overlap between nonspecific symptoms of progressive liver disease—nausea, fatigue, and abdominal pains—and Mr. A’s baseline anxiety symptoms presented new fodder for his anxiety.

His response to fluoxetine illustrated a clear dose-response relationship: His anxiety improved after each dosage increase, and symptoms escalated whenever the dosage was decreased to address a given side effect. Mr. A reported tolerable sexual side effects but ultimately nightmares were too distressing, limiting the quality of his nighttime sleep and resulting in daytime fatigue.

To address this sleep disruption and sexual side effects, fluoxetine was discontinued and Mr. A began taking nefazodone. He took up to 375 mg/d for approximately 20 months with moderate benefit, offset only somewhat by a recurrence of vivid dreams. Then case reports appeared possibly linking liver failure to nefazodone. Mr. A agreed to stop this agent and to evaluate gabapentin as an anxiolytic.

With limited dosages of gabapentin, up to a total of 1,200 mg/d, Mr. A noted significantly improved anxiety symptoms overall, but nightmares and other vivid dreams still interfered with his recovery.

No clear correlation between medication or anxiety level and severity of sleep disturbance emerged. The nature of Mr. A’s work rendered the “sleep hygiene” intervention of a regular sleep cycle impossible, and he understandably did not consider a career shift feasible. A sleep disorders consultation to address this one remaining symptom is under way.

Overall, Mr. A is delighted with his progress. He is now able to participate in informed decision making about treatment of his hepatitis, rather than merely obsess about obtaining LFTs.

Related resources

• Anxiety Disorders Association of America. www.adaa.org. Information for psychiatrists, researchers, residents, patients, caregivers, and the media
• About.com: Generalized Anxiety Disorder: A Real Illness. http://www.MentalHealth.About.com/library/mh/anx/blgadri1.htm
• National Institute of Mental Health: Anxiety Disorders http://www.nimh.nih.gov/anxiety/anxietymenu.cfm

Drug brand names

• Buspirone • Buspar
• Diazepam • Valium
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Lorazepam • Ativan
• Nefazodone • Serzone
• Nortriptyline • Pamelor
• Sertraline • Zoloft
• Trazodone • Desyrel
• Venlafaxine • Effexor

Disclosure

The author reports that he received research support from Eli Lilly and Co. and Pfizer Inc., and serves as a consultant for Eli Lilly and Co. and Ortho-McNeil Pharmaceutical.