Steroid abuse: a ‘hidden’ health hazard

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Steroid abuse: a ‘hidden’ health hazard

Initial visit: Road rage or ‘roid’ rage?

Mr. A, 25, was arrested after police interrupted an altercation between him and a senior citizen at a stoplight. He had emerged from his car, walked over to the older driver in front of him, ripped open the car door, and pulled the man out of the car and onto the street. He was still yelling at the victim when a passing officer intervened.

Mr. A was charged with assault. After a plea bargain, he was sentenced to probation and fined. He had been seeing his probation officer every 2 weeks, but his parents were worried about his erratic and sometimes defiant behavior and insisted he see a psychiatrist. He reluctantly agreed to one consultation, largely because his parents threatened to withhold financial support if he failed to do so.

The first thing the psychiatrist noticed was Mr. A’s striking muscular appearance. He was approximately 5 feet, 7 inches tall, weighed at least 200 pounds, and had a 30-inch waist and less than 10% body fat.

Dr. Carter’s and Pope’s observations

Mr. A’s diagnosis should be suspected immediately upon his entering the office. Extensive anabolic steroid use produces body changes that can be diagnosed almost at a glance. It is virtually impossible to achieve a level of muscle mass comparable to what Mr. A exhibited without the use of anabolic steroids.1

Remarkably, however, most people—including Mr. A’s parents, law enforcement personnel, and even some members of the treatment team—failed to diagnose Mr. A’s steroid use. He somehow convinced them that his extreme muscularity was the result of hard work, dedication, and scrupulous attention to diet. This suggests that steroid abuse cases involving serious violence—such as that of Mr. A—frequently go unreported and undiagnosed and are probably more common than we suspect.

Epidemiologic data suggest that clinicians should become familiar with the presentation of patients who are using anabolic steroids (Box).

Evaluation: ‘Stacking’ up

Mr. A at first vehemently denied that he had ever used anabolic steroids. After a more detailed conversation, during which the clinician demonstrated some knowledge of this area, Mr. A eventually conceded that he was taking a substantial weekly dose of the drugs at the time of the assault.

A subsequent clinical evaluation revealed that Mr. A had taken several ‘cycles’ (courses) of anabolic steroids over the last 2 to 3 years. Each cycle lasted 10 to 16 weeks and had been characterized by simultaneous use of two or more steroids, a practice known as ‘stacking.’

Mr. A started his first cycle with a modest ‘stack’ of drugs: testosterone cypionate, 200 mg twice a week, and stanozolol, 10 mg/d. Taken together, these dosages represented roughly 470 mg of testosterone equivalent per week—about 10 times the weekly secretion of testosterone in a normal male. He noticed no change in mood during this initial cycle.

With subsequent cycles, however, Mr. A became increasingly obsessed with his body image and used higher dosages. When the assault occurred, he was taking testosterone cypionate, 800 mg a week, nandrolone decanoate, 400 mg a week, and oxymetholone, 50 mg/d. With this regimen—the weekly equivalent of 1,550 mg of testosterone—Mr. A noticed prominent mood changes that met DSM-IV criteria for a manic episode. He experienced euphoria, dramatic irritability, limitless self-confidence, decreased need for sleep, distractibility, extreme recklessness (driving too fast, spending too freely), and some mildly paranoid ideation (without frank delusions). He admitted that he had twice assaulted his girlfriend and that he invariably became enraged at even the slightest annoyance when driving in traffic. He revealed that although the altercation with the older driver had led to his first arrest for ‘road rage,’ it was his third such incident.

The clinician warned Mr. A that continued steroid use could worsen his behavior—and lead to more serious trouble later on. Mr. A, however, said he was more afraid of losing muscle mass and becoming ‘small again.’ When the clinician mentioned that use of anabolic steroids without a prescription is illegal, Mr. A retorted that several of his friends had used the drugs without legal consequences.

Mr. A left the office showing no inclination to return for further treatment. The clinician could only offer to be available in the future.

Box

 

ANABOLIC STEROID ABUSE: BEYOND THE GYM

The National Household Survey on Drug Abuse, which last assessed anabolic steroid use in 1994, estimated that about 1 million Americans had used anabolic steroids at some point, with 30% of those reporting use within the previous year. Among subjects who reported use within the last 3 years, the ratio of males to females was about 13 to 1.2

Clearly, anabolic steroid abuse is no longer exclusive to professional football players and other elite male athletes. In fact, more people appear to be using anabolic steroids to improve their physiques, rather than to enhance athletic performance.3 Evidence points to increasing use by adolescents, with one survey reporting current or past use by 6.6% of male high school seniors.4

 

 

What medical sequelae await Mr. A if he continues to abuse steroids? How would you convince him to stay in treatment?

Dr. Carter’s and Pope’s observations

Mr. A’s path to mania has been well demonstrated in the literature. Hypomania or even frank manic syndromes, sometimes associated with violent behavior, are rare at weekly doses of 300 mg of testosterone equivalent. At weekly doses of >1,000 mg, psychiatric syndromes such as hypomania or mania may occur in almost one-half of cases.5

If he continues to abuse anabolic steroids, however, Mr. A could experience adverse physical reactions ranging from embarrassing acne and male-pattern baldness (Table 1) to rare and life-threatening hepatic effects such as cholestatic jaundice and peliosis hepatitis (blood-filled cysts in the liver).

Table 1

ANABOLIC STEROID ABUSE: COMMON PHYSICAL FINDINGS

 

  • Hypertrophic muscularity, disproportionately in upper torso
  • Acne on face, shoulders, and back
  • Male-pattern baldness
  • Testicular atrophy and gynecomastia in men
  • Clitoral enlargement, decreased breast size, hirsutism, and deepening of voice in women
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

The risk of atherosclerotic disease or prostate cancer later in life may also be greatly increased.

More common laboratory changes include:

 

  • increased red blood cell count, hemoglobin and hematocrit
  • elevated liver function readings (although these must not be confused with enzymes that originate from muscle tissue)
  • and unfavorable changes in triglycerides, total cholesterol, and HDL:LDL cholesterol ratios (Table 2).

Other potential laboratory changes with steroid abuse include decreased luteinizing hormone and follicle-stimulating hormone due to feedback inhibition. Feedback inhibition will also reduce testosterone and estradiol levels with use of anabolic steroids other than testosterone esters. These levels, however, would both be elevated with use of testosterone esters alone.

In men, testicular atrophy and decreased sperm count are generally reversible manifestations of steroid abuse, whereas gynecomastia may be irreversible and require surgical intervention in advanced cases.3,6 Women who use anabolic steroids (such as for body-building) are vulnerable to disrupted menstrual cycles, decreased breast size, and masculinizing effects including enlarged clitoris, hirsutism, and deepening of the voice.6

In adolescents, anabolic steroid use may cause premature closure of the epiphyses, leading to shortened stature.3

Unfortunately, warnings about these many adverse effects rarely deter anabolic steroid users such as Mr. A or persuade them to continue in treatment of any type. Most young anabolic steroid abusers report that they have never felt significant adverse effects from steroid use and know of no one who has experienced such effects. The dramatic muscle gains they have witnessed in themselves and in other users decisively outweigh what they perceive to be remote threats of adverse consequences.

Follow-up: Return to treatment

We didn’t hear from Mr. A until about 18 months later, when he unexpectedly requested a consultation.

Upon arrival, Mr. A exhibited major depression with prominent anhedonia, hypersomnia of 12 to 14 hours per night, loss of appetite, fatigue, prominent psychomotor retardation, feelings of guilt, difficulty concentrating, and suicidal thoughts (but without a frank plan). He also reported panic attacks that were randomly occurring each day, usually in public.

Mr. A conceded that he had experienced similar depressive episodes after stopping anabolic steroid use, but that they typically ran their course after 2 to 3 weeks. He said the present episode showed no sign of abating after nearly 2 months. He had attempted to ‘treat’ this episode by resuming anabolic steroid use, but he could not get an adequate supply from his dealer.

Mr. A’s total testosterone level, measured in the morning when it should be near its diurnal peak, was 127 ng/dl (normal range is 270 to 1,070 ng/dl). Physical examination revealed that his testicles had shrunk to the size of marbles (each approximately 5 mm in diameter). He was referred to an endocrinologist for evaluation and was simultaneously started on fluoxetine, 20 mg/d.

Table 2

LABORATORY ABNORMALITIES ASSOCIATED WITH ANABOLIC STEROID ABUSE

 

  • Elevated red blood cell count and hematocrit
  • Unfavorable lipid profile changes
  • Changes in LH, FSH, testosterone, and estradiol levels
  • Reduced sperm cell count
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

He returned 2 weeks later, exhibiting little improvement and wanting to resume steroids ‘because it was the only thing that really helped.’ Instead, he agreed to continue on fluoxetine and remain in follow-up. At 4 weeks, he noticed a decrease in panic attacks, return of normal mood, decreased anhedonia, and loss of suicidal ideation. He continued taking fluoxetine for another 3 months but then abruptly disappeared from treatment.

Mr. A resurfaced about 1 year later, revealing to the psychiatrist that he had taken yet another cycle of anabolic steroids, largely because he feared losing his muscle mass. His panic attacks had recurred almost immediately when he began tapering down from the peak of this cycle, and he agreed to resume taking fluoxetine.

 

 

A look at Mr. A’s extended history may provide clues to his persistent anabolic steroid abuse problem. He had displayed prominent symptoms of conduct disorder as a child. He had been truant from school, had occasionally run away from home, and had been involved in several misdemeanors. While in high school, he typically drank 10 to 12 beers over a weekend and had experimented with hallucinogenic mushrooms and 3,4-methylenedioxymethamphetamine (‘ecstasy’).

He started weightlifting while in high school and by age 17 was visiting the gym every day. He began college on a football scholarship but dropped out after 1 year. Starting in his early 20s, he competed in several bodybuilding contests.

Despite his impressive muscularity, Mr. A was anxious about his body appearance. He often would not take off his shirt—even when at the beach or a swimming pool—for fear that he would appear too small. He sometimes wore heavy sweatpants in the sweltering heat to conceal his legs. He also admitted spending as much as 2 hours a day examining himself in the mirror. ‘Sometimes when I get a bad (look at) myself, I will refuse to go out for the rest of the day,’ he said.

Mr. A has had a succession of girlfriends, but his rigid commitment to diet and exercise invariably ended these relationships.

At this point, would you first address Mr. A’s apparent substance use problem or the underlying body dysmorphic symptoms?

Dr. Carter’s and Pope’s observations

Two comorbidities noted here—substance abuse and body dysmorphic disorder—are common among anabolic steroid abusers. Addressing these problems, especially the body dysmorphic disorder, may sometimes help patients who are unwilling to address their steroid use directly. Body dysmorphic disorder may respond to selective serotonin reuptake inhibitors7 and cognitive-behavioral therapy.8

Anabolic steroids are not associated with immediate intoxicating effects, and ICD-10 categorizes them as substances not associated with dependence. After prolonged use at high doses, however, anabolic steroids are often associated with euphoria. Researchers also have found that some steroid abusers do meet DSM-IV criteria for substance dependence.6

Beyond the direct psychotropic effects of anabolic steroids, the depressive symptoms commonly seen during their withdrawal may perpetuate the dependence, as was the case with Mr. A. Most depressive symptoms that follow steroid cessation do not require drug therapy,3 but Mr. A developed severe and persistent depressive symptoms, complicated by panic disorder and body image concerns at a level diagnostic of body dysmorphic disorder. Such body image concerns often precipitate relapse into steroid use.

Conclusion: Another setback

As of this writing, Mr. A is again lost to follow-up. After taking fluoxetine and keeping monthly appointments for about 6 months, he failed to arrive for a visit and did not set another appointment. The patient may have once again stopped medication and embarked on yet another cycle of anabolic steroid use. If this is so, we can only hope that he returns to treatment before it is too late.

Related resource

  • Lukas SE. Steroids. Hillside, NJ: Enslow Publishers, 1994.

Drug brand names

 

  • Fluoxetine • Prozac
  • Nandrolone decanoate • Deca-Durabolin
  • Oxymetholone • Anadrol
  • Stanozolol • Winstrol

Disclosure

Dr. Carter reports that he receives research/grant support from or is a consultant to Eli Lilly and Co., Pfizer Inc., and Ortho-McNeil Pharmaceutical.

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

References

 

1. Kouri E, Pope HG, Jr, Katz DL, Oliva P. Fat free mass index in users and non-users of anabolic-androgenic steroids. Clin J Sport Med 1995;5:223-8.

2. National Household Survey on Drug Abuse, 1994: http://www.icpsr.umich.edu.

3. Pope HG, Jr, Brower KJ. Anabolic-androgenic steroid abuse. In: Sadock BJ, Sadock VA (eds). Comprehensive textbook of psychiatry (7th ed). Philadelphia: Lippincott Williams & Wilkins, 2000;1085-95.

4. Buckley WA, Yesalis CE, 3rd, Friedl KE, et al. Estimated prevalence of anabolic steroid use among male high school seniors. JAMA 1988;260(23):3441-5.

5. Pope HG, Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. Arch Gen Psychiatry 1994;51:375-82.

6. Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

7. Phillips KA. Pharmacologic treatment of body dysmorphic disorder: A review of empirical data and a proposed treatment algorithm. Psychiatr Clin North Am 2000;7:59-82.

8. Rosen JC, Reiter J, Orosan P. Cognitive/behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol 1995;63:2639.-

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Initial visit: Road rage or ‘roid’ rage?

Mr. A, 25, was arrested after police interrupted an altercation between him and a senior citizen at a stoplight. He had emerged from his car, walked over to the older driver in front of him, ripped open the car door, and pulled the man out of the car and onto the street. He was still yelling at the victim when a passing officer intervened.

Mr. A was charged with assault. After a plea bargain, he was sentenced to probation and fined. He had been seeing his probation officer every 2 weeks, but his parents were worried about his erratic and sometimes defiant behavior and insisted he see a psychiatrist. He reluctantly agreed to one consultation, largely because his parents threatened to withhold financial support if he failed to do so.

The first thing the psychiatrist noticed was Mr. A’s striking muscular appearance. He was approximately 5 feet, 7 inches tall, weighed at least 200 pounds, and had a 30-inch waist and less than 10% body fat.

Dr. Carter’s and Pope’s observations

Mr. A’s diagnosis should be suspected immediately upon his entering the office. Extensive anabolic steroid use produces body changes that can be diagnosed almost at a glance. It is virtually impossible to achieve a level of muscle mass comparable to what Mr. A exhibited without the use of anabolic steroids.1

Remarkably, however, most people—including Mr. A’s parents, law enforcement personnel, and even some members of the treatment team—failed to diagnose Mr. A’s steroid use. He somehow convinced them that his extreme muscularity was the result of hard work, dedication, and scrupulous attention to diet. This suggests that steroid abuse cases involving serious violence—such as that of Mr. A—frequently go unreported and undiagnosed and are probably more common than we suspect.

Epidemiologic data suggest that clinicians should become familiar with the presentation of patients who are using anabolic steroids (Box).

Evaluation: ‘Stacking’ up

Mr. A at first vehemently denied that he had ever used anabolic steroids. After a more detailed conversation, during which the clinician demonstrated some knowledge of this area, Mr. A eventually conceded that he was taking a substantial weekly dose of the drugs at the time of the assault.

A subsequent clinical evaluation revealed that Mr. A had taken several ‘cycles’ (courses) of anabolic steroids over the last 2 to 3 years. Each cycle lasted 10 to 16 weeks and had been characterized by simultaneous use of two or more steroids, a practice known as ‘stacking.’

Mr. A started his first cycle with a modest ‘stack’ of drugs: testosterone cypionate, 200 mg twice a week, and stanozolol, 10 mg/d. Taken together, these dosages represented roughly 470 mg of testosterone equivalent per week—about 10 times the weekly secretion of testosterone in a normal male. He noticed no change in mood during this initial cycle.

With subsequent cycles, however, Mr. A became increasingly obsessed with his body image and used higher dosages. When the assault occurred, he was taking testosterone cypionate, 800 mg a week, nandrolone decanoate, 400 mg a week, and oxymetholone, 50 mg/d. With this regimen—the weekly equivalent of 1,550 mg of testosterone—Mr. A noticed prominent mood changes that met DSM-IV criteria for a manic episode. He experienced euphoria, dramatic irritability, limitless self-confidence, decreased need for sleep, distractibility, extreme recklessness (driving too fast, spending too freely), and some mildly paranoid ideation (without frank delusions). He admitted that he had twice assaulted his girlfriend and that he invariably became enraged at even the slightest annoyance when driving in traffic. He revealed that although the altercation with the older driver had led to his first arrest for ‘road rage,’ it was his third such incident.

The clinician warned Mr. A that continued steroid use could worsen his behavior—and lead to more serious trouble later on. Mr. A, however, said he was more afraid of losing muscle mass and becoming ‘small again.’ When the clinician mentioned that use of anabolic steroids without a prescription is illegal, Mr. A retorted that several of his friends had used the drugs without legal consequences.

Mr. A left the office showing no inclination to return for further treatment. The clinician could only offer to be available in the future.

Box

 

ANABOLIC STEROID ABUSE: BEYOND THE GYM

The National Household Survey on Drug Abuse, which last assessed anabolic steroid use in 1994, estimated that about 1 million Americans had used anabolic steroids at some point, with 30% of those reporting use within the previous year. Among subjects who reported use within the last 3 years, the ratio of males to females was about 13 to 1.2

Clearly, anabolic steroid abuse is no longer exclusive to professional football players and other elite male athletes. In fact, more people appear to be using anabolic steroids to improve their physiques, rather than to enhance athletic performance.3 Evidence points to increasing use by adolescents, with one survey reporting current or past use by 6.6% of male high school seniors.4

 

 

What medical sequelae await Mr. A if he continues to abuse steroids? How would you convince him to stay in treatment?

Dr. Carter’s and Pope’s observations

Mr. A’s path to mania has been well demonstrated in the literature. Hypomania or even frank manic syndromes, sometimes associated with violent behavior, are rare at weekly doses of 300 mg of testosterone equivalent. At weekly doses of >1,000 mg, psychiatric syndromes such as hypomania or mania may occur in almost one-half of cases.5

If he continues to abuse anabolic steroids, however, Mr. A could experience adverse physical reactions ranging from embarrassing acne and male-pattern baldness (Table 1) to rare and life-threatening hepatic effects such as cholestatic jaundice and peliosis hepatitis (blood-filled cysts in the liver).

Table 1

ANABOLIC STEROID ABUSE: COMMON PHYSICAL FINDINGS

 

  • Hypertrophic muscularity, disproportionately in upper torso
  • Acne on face, shoulders, and back
  • Male-pattern baldness
  • Testicular atrophy and gynecomastia in men
  • Clitoral enlargement, decreased breast size, hirsutism, and deepening of voice in women
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

The risk of atherosclerotic disease or prostate cancer later in life may also be greatly increased.

More common laboratory changes include:

 

  • increased red blood cell count, hemoglobin and hematocrit
  • elevated liver function readings (although these must not be confused with enzymes that originate from muscle tissue)
  • and unfavorable changes in triglycerides, total cholesterol, and HDL:LDL cholesterol ratios (Table 2).

Other potential laboratory changes with steroid abuse include decreased luteinizing hormone and follicle-stimulating hormone due to feedback inhibition. Feedback inhibition will also reduce testosterone and estradiol levels with use of anabolic steroids other than testosterone esters. These levels, however, would both be elevated with use of testosterone esters alone.

In men, testicular atrophy and decreased sperm count are generally reversible manifestations of steroid abuse, whereas gynecomastia may be irreversible and require surgical intervention in advanced cases.3,6 Women who use anabolic steroids (such as for body-building) are vulnerable to disrupted menstrual cycles, decreased breast size, and masculinizing effects including enlarged clitoris, hirsutism, and deepening of the voice.6

In adolescents, anabolic steroid use may cause premature closure of the epiphyses, leading to shortened stature.3

Unfortunately, warnings about these many adverse effects rarely deter anabolic steroid users such as Mr. A or persuade them to continue in treatment of any type. Most young anabolic steroid abusers report that they have never felt significant adverse effects from steroid use and know of no one who has experienced such effects. The dramatic muscle gains they have witnessed in themselves and in other users decisively outweigh what they perceive to be remote threats of adverse consequences.

Follow-up: Return to treatment

We didn’t hear from Mr. A until about 18 months later, when he unexpectedly requested a consultation.

Upon arrival, Mr. A exhibited major depression with prominent anhedonia, hypersomnia of 12 to 14 hours per night, loss of appetite, fatigue, prominent psychomotor retardation, feelings of guilt, difficulty concentrating, and suicidal thoughts (but without a frank plan). He also reported panic attacks that were randomly occurring each day, usually in public.

Mr. A conceded that he had experienced similar depressive episodes after stopping anabolic steroid use, but that they typically ran their course after 2 to 3 weeks. He said the present episode showed no sign of abating after nearly 2 months. He had attempted to ‘treat’ this episode by resuming anabolic steroid use, but he could not get an adequate supply from his dealer.

Mr. A’s total testosterone level, measured in the morning when it should be near its diurnal peak, was 127 ng/dl (normal range is 270 to 1,070 ng/dl). Physical examination revealed that his testicles had shrunk to the size of marbles (each approximately 5 mm in diameter). He was referred to an endocrinologist for evaluation and was simultaneously started on fluoxetine, 20 mg/d.

Table 2

LABORATORY ABNORMALITIES ASSOCIATED WITH ANABOLIC STEROID ABUSE

 

  • Elevated red blood cell count and hematocrit
  • Unfavorable lipid profile changes
  • Changes in LH, FSH, testosterone, and estradiol levels
  • Reduced sperm cell count
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

He returned 2 weeks later, exhibiting little improvement and wanting to resume steroids ‘because it was the only thing that really helped.’ Instead, he agreed to continue on fluoxetine and remain in follow-up. At 4 weeks, he noticed a decrease in panic attacks, return of normal mood, decreased anhedonia, and loss of suicidal ideation. He continued taking fluoxetine for another 3 months but then abruptly disappeared from treatment.

Mr. A resurfaced about 1 year later, revealing to the psychiatrist that he had taken yet another cycle of anabolic steroids, largely because he feared losing his muscle mass. His panic attacks had recurred almost immediately when he began tapering down from the peak of this cycle, and he agreed to resume taking fluoxetine.

 

 

A look at Mr. A’s extended history may provide clues to his persistent anabolic steroid abuse problem. He had displayed prominent symptoms of conduct disorder as a child. He had been truant from school, had occasionally run away from home, and had been involved in several misdemeanors. While in high school, he typically drank 10 to 12 beers over a weekend and had experimented with hallucinogenic mushrooms and 3,4-methylenedioxymethamphetamine (‘ecstasy’).

He started weightlifting while in high school and by age 17 was visiting the gym every day. He began college on a football scholarship but dropped out after 1 year. Starting in his early 20s, he competed in several bodybuilding contests.

Despite his impressive muscularity, Mr. A was anxious about his body appearance. He often would not take off his shirt—even when at the beach or a swimming pool—for fear that he would appear too small. He sometimes wore heavy sweatpants in the sweltering heat to conceal his legs. He also admitted spending as much as 2 hours a day examining himself in the mirror. ‘Sometimes when I get a bad (look at) myself, I will refuse to go out for the rest of the day,’ he said.

Mr. A has had a succession of girlfriends, but his rigid commitment to diet and exercise invariably ended these relationships.

At this point, would you first address Mr. A’s apparent substance use problem or the underlying body dysmorphic symptoms?

Dr. Carter’s and Pope’s observations

Two comorbidities noted here—substance abuse and body dysmorphic disorder—are common among anabolic steroid abusers. Addressing these problems, especially the body dysmorphic disorder, may sometimes help patients who are unwilling to address their steroid use directly. Body dysmorphic disorder may respond to selective serotonin reuptake inhibitors7 and cognitive-behavioral therapy.8

Anabolic steroids are not associated with immediate intoxicating effects, and ICD-10 categorizes them as substances not associated with dependence. After prolonged use at high doses, however, anabolic steroids are often associated with euphoria. Researchers also have found that some steroid abusers do meet DSM-IV criteria for substance dependence.6

Beyond the direct psychotropic effects of anabolic steroids, the depressive symptoms commonly seen during their withdrawal may perpetuate the dependence, as was the case with Mr. A. Most depressive symptoms that follow steroid cessation do not require drug therapy,3 but Mr. A developed severe and persistent depressive symptoms, complicated by panic disorder and body image concerns at a level diagnostic of body dysmorphic disorder. Such body image concerns often precipitate relapse into steroid use.

Conclusion: Another setback

As of this writing, Mr. A is again lost to follow-up. After taking fluoxetine and keeping monthly appointments for about 6 months, he failed to arrive for a visit and did not set another appointment. The patient may have once again stopped medication and embarked on yet another cycle of anabolic steroid use. If this is so, we can only hope that he returns to treatment before it is too late.

Related resource

  • Lukas SE. Steroids. Hillside, NJ: Enslow Publishers, 1994.

Drug brand names

 

  • Fluoxetine • Prozac
  • Nandrolone decanoate • Deca-Durabolin
  • Oxymetholone • Anadrol
  • Stanozolol • Winstrol

Disclosure

Dr. Carter reports that he receives research/grant support from or is a consultant to Eli Lilly and Co., Pfizer Inc., and Ortho-McNeil Pharmaceutical.

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

Initial visit: Road rage or ‘roid’ rage?

Mr. A, 25, was arrested after police interrupted an altercation between him and a senior citizen at a stoplight. He had emerged from his car, walked over to the older driver in front of him, ripped open the car door, and pulled the man out of the car and onto the street. He was still yelling at the victim when a passing officer intervened.

Mr. A was charged with assault. After a plea bargain, he was sentenced to probation and fined. He had been seeing his probation officer every 2 weeks, but his parents were worried about his erratic and sometimes defiant behavior and insisted he see a psychiatrist. He reluctantly agreed to one consultation, largely because his parents threatened to withhold financial support if he failed to do so.

The first thing the psychiatrist noticed was Mr. A’s striking muscular appearance. He was approximately 5 feet, 7 inches tall, weighed at least 200 pounds, and had a 30-inch waist and less than 10% body fat.

Dr. Carter’s and Pope’s observations

Mr. A’s diagnosis should be suspected immediately upon his entering the office. Extensive anabolic steroid use produces body changes that can be diagnosed almost at a glance. It is virtually impossible to achieve a level of muscle mass comparable to what Mr. A exhibited without the use of anabolic steroids.1

Remarkably, however, most people—including Mr. A’s parents, law enforcement personnel, and even some members of the treatment team—failed to diagnose Mr. A’s steroid use. He somehow convinced them that his extreme muscularity was the result of hard work, dedication, and scrupulous attention to diet. This suggests that steroid abuse cases involving serious violence—such as that of Mr. A—frequently go unreported and undiagnosed and are probably more common than we suspect.

Epidemiologic data suggest that clinicians should become familiar with the presentation of patients who are using anabolic steroids (Box).

Evaluation: ‘Stacking’ up

Mr. A at first vehemently denied that he had ever used anabolic steroids. After a more detailed conversation, during which the clinician demonstrated some knowledge of this area, Mr. A eventually conceded that he was taking a substantial weekly dose of the drugs at the time of the assault.

A subsequent clinical evaluation revealed that Mr. A had taken several ‘cycles’ (courses) of anabolic steroids over the last 2 to 3 years. Each cycle lasted 10 to 16 weeks and had been characterized by simultaneous use of two or more steroids, a practice known as ‘stacking.’

Mr. A started his first cycle with a modest ‘stack’ of drugs: testosterone cypionate, 200 mg twice a week, and stanozolol, 10 mg/d. Taken together, these dosages represented roughly 470 mg of testosterone equivalent per week—about 10 times the weekly secretion of testosterone in a normal male. He noticed no change in mood during this initial cycle.

With subsequent cycles, however, Mr. A became increasingly obsessed with his body image and used higher dosages. When the assault occurred, he was taking testosterone cypionate, 800 mg a week, nandrolone decanoate, 400 mg a week, and oxymetholone, 50 mg/d. With this regimen—the weekly equivalent of 1,550 mg of testosterone—Mr. A noticed prominent mood changes that met DSM-IV criteria for a manic episode. He experienced euphoria, dramatic irritability, limitless self-confidence, decreased need for sleep, distractibility, extreme recklessness (driving too fast, spending too freely), and some mildly paranoid ideation (without frank delusions). He admitted that he had twice assaulted his girlfriend and that he invariably became enraged at even the slightest annoyance when driving in traffic. He revealed that although the altercation with the older driver had led to his first arrest for ‘road rage,’ it was his third such incident.

The clinician warned Mr. A that continued steroid use could worsen his behavior—and lead to more serious trouble later on. Mr. A, however, said he was more afraid of losing muscle mass and becoming ‘small again.’ When the clinician mentioned that use of anabolic steroids without a prescription is illegal, Mr. A retorted that several of his friends had used the drugs without legal consequences.

Mr. A left the office showing no inclination to return for further treatment. The clinician could only offer to be available in the future.

Box

 

ANABOLIC STEROID ABUSE: BEYOND THE GYM

The National Household Survey on Drug Abuse, which last assessed anabolic steroid use in 1994, estimated that about 1 million Americans had used anabolic steroids at some point, with 30% of those reporting use within the previous year. Among subjects who reported use within the last 3 years, the ratio of males to females was about 13 to 1.2

Clearly, anabolic steroid abuse is no longer exclusive to professional football players and other elite male athletes. In fact, more people appear to be using anabolic steroids to improve their physiques, rather than to enhance athletic performance.3 Evidence points to increasing use by adolescents, with one survey reporting current or past use by 6.6% of male high school seniors.4

 

 

What medical sequelae await Mr. A if he continues to abuse steroids? How would you convince him to stay in treatment?

Dr. Carter’s and Pope’s observations

Mr. A’s path to mania has been well demonstrated in the literature. Hypomania or even frank manic syndromes, sometimes associated with violent behavior, are rare at weekly doses of 300 mg of testosterone equivalent. At weekly doses of >1,000 mg, psychiatric syndromes such as hypomania or mania may occur in almost one-half of cases.5

If he continues to abuse anabolic steroids, however, Mr. A could experience adverse physical reactions ranging from embarrassing acne and male-pattern baldness (Table 1) to rare and life-threatening hepatic effects such as cholestatic jaundice and peliosis hepatitis (blood-filled cysts in the liver).

Table 1

ANABOLIC STEROID ABUSE: COMMON PHYSICAL FINDINGS

 

  • Hypertrophic muscularity, disproportionately in upper torso
  • Acne on face, shoulders, and back
  • Male-pattern baldness
  • Testicular atrophy and gynecomastia in men
  • Clitoral enlargement, decreased breast size, hirsutism, and deepening of voice in women
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

The risk of atherosclerotic disease or prostate cancer later in life may also be greatly increased.

More common laboratory changes include:

 

  • increased red blood cell count, hemoglobin and hematocrit
  • elevated liver function readings (although these must not be confused with enzymes that originate from muscle tissue)
  • and unfavorable changes in triglycerides, total cholesterol, and HDL:LDL cholesterol ratios (Table 2).

Other potential laboratory changes with steroid abuse include decreased luteinizing hormone and follicle-stimulating hormone due to feedback inhibition. Feedback inhibition will also reduce testosterone and estradiol levels with use of anabolic steroids other than testosterone esters. These levels, however, would both be elevated with use of testosterone esters alone.

In men, testicular atrophy and decreased sperm count are generally reversible manifestations of steroid abuse, whereas gynecomastia may be irreversible and require surgical intervention in advanced cases.3,6 Women who use anabolic steroids (such as for body-building) are vulnerable to disrupted menstrual cycles, decreased breast size, and masculinizing effects including enlarged clitoris, hirsutism, and deepening of the voice.6

In adolescents, anabolic steroid use may cause premature closure of the epiphyses, leading to shortened stature.3

Unfortunately, warnings about these many adverse effects rarely deter anabolic steroid users such as Mr. A or persuade them to continue in treatment of any type. Most young anabolic steroid abusers report that they have never felt significant adverse effects from steroid use and know of no one who has experienced such effects. The dramatic muscle gains they have witnessed in themselves and in other users decisively outweigh what they perceive to be remote threats of adverse consequences.

Follow-up: Return to treatment

We didn’t hear from Mr. A until about 18 months later, when he unexpectedly requested a consultation.

Upon arrival, Mr. A exhibited major depression with prominent anhedonia, hypersomnia of 12 to 14 hours per night, loss of appetite, fatigue, prominent psychomotor retardation, feelings of guilt, difficulty concentrating, and suicidal thoughts (but without a frank plan). He also reported panic attacks that were randomly occurring each day, usually in public.

Mr. A conceded that he had experienced similar depressive episodes after stopping anabolic steroid use, but that they typically ran their course after 2 to 3 weeks. He said the present episode showed no sign of abating after nearly 2 months. He had attempted to ‘treat’ this episode by resuming anabolic steroid use, but he could not get an adequate supply from his dealer.

Mr. A’s total testosterone level, measured in the morning when it should be near its diurnal peak, was 127 ng/dl (normal range is 270 to 1,070 ng/dl). Physical examination revealed that his testicles had shrunk to the size of marbles (each approximately 5 mm in diameter). He was referred to an endocrinologist for evaluation and was simultaneously started on fluoxetine, 20 mg/d.

Table 2

LABORATORY ABNORMALITIES ASSOCIATED WITH ANABOLIC STEROID ABUSE

 

  • Elevated red blood cell count and hematocrit
  • Unfavorable lipid profile changes
  • Changes in LH, FSH, testosterone, and estradiol levels
  • Reduced sperm cell count
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

He returned 2 weeks later, exhibiting little improvement and wanting to resume steroids ‘because it was the only thing that really helped.’ Instead, he agreed to continue on fluoxetine and remain in follow-up. At 4 weeks, he noticed a decrease in panic attacks, return of normal mood, decreased anhedonia, and loss of suicidal ideation. He continued taking fluoxetine for another 3 months but then abruptly disappeared from treatment.

Mr. A resurfaced about 1 year later, revealing to the psychiatrist that he had taken yet another cycle of anabolic steroids, largely because he feared losing his muscle mass. His panic attacks had recurred almost immediately when he began tapering down from the peak of this cycle, and he agreed to resume taking fluoxetine.

 

 

A look at Mr. A’s extended history may provide clues to his persistent anabolic steroid abuse problem. He had displayed prominent symptoms of conduct disorder as a child. He had been truant from school, had occasionally run away from home, and had been involved in several misdemeanors. While in high school, he typically drank 10 to 12 beers over a weekend and had experimented with hallucinogenic mushrooms and 3,4-methylenedioxymethamphetamine (‘ecstasy’).

He started weightlifting while in high school and by age 17 was visiting the gym every day. He began college on a football scholarship but dropped out after 1 year. Starting in his early 20s, he competed in several bodybuilding contests.

Despite his impressive muscularity, Mr. A was anxious about his body appearance. He often would not take off his shirt—even when at the beach or a swimming pool—for fear that he would appear too small. He sometimes wore heavy sweatpants in the sweltering heat to conceal his legs. He also admitted spending as much as 2 hours a day examining himself in the mirror. ‘Sometimes when I get a bad (look at) myself, I will refuse to go out for the rest of the day,’ he said.

Mr. A has had a succession of girlfriends, but his rigid commitment to diet and exercise invariably ended these relationships.

At this point, would you first address Mr. A’s apparent substance use problem or the underlying body dysmorphic symptoms?

Dr. Carter’s and Pope’s observations

Two comorbidities noted here—substance abuse and body dysmorphic disorder—are common among anabolic steroid abusers. Addressing these problems, especially the body dysmorphic disorder, may sometimes help patients who are unwilling to address their steroid use directly. Body dysmorphic disorder may respond to selective serotonin reuptake inhibitors7 and cognitive-behavioral therapy.8

Anabolic steroids are not associated with immediate intoxicating effects, and ICD-10 categorizes them as substances not associated with dependence. After prolonged use at high doses, however, anabolic steroids are often associated with euphoria. Researchers also have found that some steroid abusers do meet DSM-IV criteria for substance dependence.6

Beyond the direct psychotropic effects of anabolic steroids, the depressive symptoms commonly seen during their withdrawal may perpetuate the dependence, as was the case with Mr. A. Most depressive symptoms that follow steroid cessation do not require drug therapy,3 but Mr. A developed severe and persistent depressive symptoms, complicated by panic disorder and body image concerns at a level diagnostic of body dysmorphic disorder. Such body image concerns often precipitate relapse into steroid use.

Conclusion: Another setback

As of this writing, Mr. A is again lost to follow-up. After taking fluoxetine and keeping monthly appointments for about 6 months, he failed to arrive for a visit and did not set another appointment. The patient may have once again stopped medication and embarked on yet another cycle of anabolic steroid use. If this is so, we can only hope that he returns to treatment before it is too late.

Related resource

  • Lukas SE. Steroids. Hillside, NJ: Enslow Publishers, 1994.

Drug brand names

 

  • Fluoxetine • Prozac
  • Nandrolone decanoate • Deca-Durabolin
  • Oxymetholone • Anadrol
  • Stanozolol • Winstrol

Disclosure

Dr. Carter reports that he receives research/grant support from or is a consultant to Eli Lilly and Co., Pfizer Inc., and Ortho-McNeil Pharmaceutical.

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

References

 

1. Kouri E, Pope HG, Jr, Katz DL, Oliva P. Fat free mass index in users and non-users of anabolic-androgenic steroids. Clin J Sport Med 1995;5:223-8.

2. National Household Survey on Drug Abuse, 1994: http://www.icpsr.umich.edu.

3. Pope HG, Jr, Brower KJ. Anabolic-androgenic steroid abuse. In: Sadock BJ, Sadock VA (eds). Comprehensive textbook of psychiatry (7th ed). Philadelphia: Lippincott Williams & Wilkins, 2000;1085-95.

4. Buckley WA, Yesalis CE, 3rd, Friedl KE, et al. Estimated prevalence of anabolic steroid use among male high school seniors. JAMA 1988;260(23):3441-5.

5. Pope HG, Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. Arch Gen Psychiatry 1994;51:375-82.

6. Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

7. Phillips KA. Pharmacologic treatment of body dysmorphic disorder: A review of empirical data and a proposed treatment algorithm. Psychiatr Clin North Am 2000;7:59-82.

8. Rosen JC, Reiter J, Orosan P. Cognitive/behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol 1995;63:2639.-

References

 

1. Kouri E, Pope HG, Jr, Katz DL, Oliva P. Fat free mass index in users and non-users of anabolic-androgenic steroids. Clin J Sport Med 1995;5:223-8.

2. National Household Survey on Drug Abuse, 1994: http://www.icpsr.umich.edu.

3. Pope HG, Jr, Brower KJ. Anabolic-androgenic steroid abuse. In: Sadock BJ, Sadock VA (eds). Comprehensive textbook of psychiatry (7th ed). Philadelphia: Lippincott Williams & Wilkins, 2000;1085-95.

4. Buckley WA, Yesalis CE, 3rd, Friedl KE, et al. Estimated prevalence of anabolic steroid use among male high school seniors. JAMA 1988;260(23):3441-5.

5. Pope HG, Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. Arch Gen Psychiatry 1994;51:375-82.

6. Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

7. Phillips KA. Pharmacologic treatment of body dysmorphic disorder: A review of empirical data and a proposed treatment algorithm. Psychiatr Clin North Am 2000;7:59-82.

8. Rosen JC, Reiter J, Orosan P. Cognitive/behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol 1995;63:2639.-

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Initial visit: Road rage or ‘roid’ rage?

Mr. A, 25, was arrested after police interrupted an altercation between him and a senior citizen at a stoplight. He had emerged from his car, walked over to the older driver in front of him, ripped open the car door, and pulled the man out of the car and onto the street. He was still yelling at the victim when a passing officer intervened.

Mr. A was charged with assault. After a plea bargain, he was sentenced to probation and fined. He had been seeing his probation officer every 2 weeks, but his parents were worried about his erratic and sometimes defiant behavior and insisted he see a psychiatrist. He reluctantly agreed to one consultation, largely because his parents threatened to withhold financial support if he failed to do so.

The first thing the psychiatrist noticed was Mr. A’s striking muscular appearance. He was approximately 5 feet, 7 inches tall, weighed at least 200 pounds, and had a 30-inch waist and less than 10% body fat.

Dr. Carter’s and Pope’s observations

Mr. A’s diagnosis should be suspected immediately upon his entering the office. Extensive anabolic steroid use produces body changes that can be diagnosed almost at a glance. It is virtually impossible to achieve a level of muscle mass comparable to what Mr. A exhibited without the use of anabolic steroids.1

Remarkably, however, most people—including Mr. A’s parents, law enforcement personnel, and even some members of the treatment team—failed to diagnose Mr. A’s steroid use. He somehow convinced them that his extreme muscularity was the result of hard work, dedication, and scrupulous attention to diet. This suggests that steroid abuse cases involving serious violence—such as that of Mr. A—frequently go unreported and undiagnosed and are probably more common than we suspect.

Epidemiologic data suggest that clinicians should become familiar with the presentation of patients who are using anabolic steroids (Box).

Evaluation: ‘Stacking’ up

Mr. A at first vehemently denied that he had ever used anabolic steroids. After a more detailed conversation, during which the clinician demonstrated some knowledge of this area, Mr. A eventually conceded that he was taking a substantial weekly dose of the drugs at the time of the assault.

A subsequent clinical evaluation revealed that Mr. A had taken several ‘cycles’ (courses) of anabolic steroids over the last 2 to 3 years. Each cycle lasted 10 to 16 weeks and had been characterized by simultaneous use of two or more steroids, a practice known as ‘stacking.’

Mr. A started his first cycle with a modest ‘stack’ of drugs: testosterone cypionate, 200 mg twice a week, and stanozolol, 10 mg/d. Taken together, these dosages represented roughly 470 mg of testosterone equivalent per week—about 10 times the weekly secretion of testosterone in a normal male. He noticed no change in mood during this initial cycle.

With subsequent cycles, however, Mr. A became increasingly obsessed with his body image and used higher dosages. When the assault occurred, he was taking testosterone cypionate, 800 mg a week, nandrolone decanoate, 400 mg a week, and oxymetholone, 50 mg/d. With this regimen—the weekly equivalent of 1,550 mg of testosterone—Mr. A noticed prominent mood changes that met DSM-IV criteria for a manic episode. He experienced euphoria, dramatic irritability, limitless self-confidence, decreased need for sleep, distractibility, extreme recklessness (driving too fast, spending too freely), and some mildly paranoid ideation (without frank delusions). He admitted that he had twice assaulted his girlfriend and that he invariably became enraged at even the slightest annoyance when driving in traffic. He revealed that although the altercation with the older driver had led to his first arrest for ‘road rage,’ it was his third such incident.

The clinician warned Mr. A that continued steroid use could worsen his behavior—and lead to more serious trouble later on. Mr. A, however, said he was more afraid of losing muscle mass and becoming ‘small again.’ When the clinician mentioned that use of anabolic steroids without a prescription is illegal, Mr. A retorted that several of his friends had used the drugs without legal consequences.

Mr. A left the office showing no inclination to return for further treatment. The clinician could only offer to be available in the future.

Box

 

ANABOLIC STEROID ABUSE: BEYOND THE GYM

The National Household Survey on Drug Abuse, which last assessed anabolic steroid use in 1994, estimated that about 1 million Americans had used anabolic steroids at some point, with 30% of those reporting use within the previous year. Among subjects who reported use within the last 3 years, the ratio of males to females was about 13 to 1.2

Clearly, anabolic steroid abuse is no longer exclusive to professional football players and other elite male athletes. In fact, more people appear to be using anabolic steroids to improve their physiques, rather than to enhance athletic performance.3 Evidence points to increasing use by adolescents, with one survey reporting current or past use by 6.6% of male high school seniors.4

 

 

What medical sequelae await Mr. A if he continues to abuse steroids? How would you convince him to stay in treatment?

Dr. Carter’s and Pope’s observations

Mr. A’s path to mania has been well demonstrated in the literature. Hypomania or even frank manic syndromes, sometimes associated with violent behavior, are rare at weekly doses of 300 mg of testosterone equivalent. At weekly doses of >1,000 mg, psychiatric syndromes such as hypomania or mania may occur in almost one-half of cases.5

If he continues to abuse anabolic steroids, however, Mr. A could experience adverse physical reactions ranging from embarrassing acne and male-pattern baldness (Table 1) to rare and life-threatening hepatic effects such as cholestatic jaundice and peliosis hepatitis (blood-filled cysts in the liver).

Table 1

ANABOLIC STEROID ABUSE: COMMON PHYSICAL FINDINGS

 

  • Hypertrophic muscularity, disproportionately in upper torso
  • Acne on face, shoulders, and back
  • Male-pattern baldness
  • Testicular atrophy and gynecomastia in men
  • Clitoral enlargement, decreased breast size, hirsutism, and deepening of voice in women
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

The risk of atherosclerotic disease or prostate cancer later in life may also be greatly increased.

More common laboratory changes include:

 

  • increased red blood cell count, hemoglobin and hematocrit
  • elevated liver function readings (although these must not be confused with enzymes that originate from muscle tissue)
  • and unfavorable changes in triglycerides, total cholesterol, and HDL:LDL cholesterol ratios (Table 2).

Other potential laboratory changes with steroid abuse include decreased luteinizing hormone and follicle-stimulating hormone due to feedback inhibition. Feedback inhibition will also reduce testosterone and estradiol levels with use of anabolic steroids other than testosterone esters. These levels, however, would both be elevated with use of testosterone esters alone.

In men, testicular atrophy and decreased sperm count are generally reversible manifestations of steroid abuse, whereas gynecomastia may be irreversible and require surgical intervention in advanced cases.3,6 Women who use anabolic steroids (such as for body-building) are vulnerable to disrupted menstrual cycles, decreased breast size, and masculinizing effects including enlarged clitoris, hirsutism, and deepening of the voice.6

In adolescents, anabolic steroid use may cause premature closure of the epiphyses, leading to shortened stature.3

Unfortunately, warnings about these many adverse effects rarely deter anabolic steroid users such as Mr. A or persuade them to continue in treatment of any type. Most young anabolic steroid abusers report that they have never felt significant adverse effects from steroid use and know of no one who has experienced such effects. The dramatic muscle gains they have witnessed in themselves and in other users decisively outweigh what they perceive to be remote threats of adverse consequences.

Follow-up: Return to treatment

We didn’t hear from Mr. A until about 18 months later, when he unexpectedly requested a consultation.

Upon arrival, Mr. A exhibited major depression with prominent anhedonia, hypersomnia of 12 to 14 hours per night, loss of appetite, fatigue, prominent psychomotor retardation, feelings of guilt, difficulty concentrating, and suicidal thoughts (but without a frank plan). He also reported panic attacks that were randomly occurring each day, usually in public.

Mr. A conceded that he had experienced similar depressive episodes after stopping anabolic steroid use, but that they typically ran their course after 2 to 3 weeks. He said the present episode showed no sign of abating after nearly 2 months. He had attempted to ‘treat’ this episode by resuming anabolic steroid use, but he could not get an adequate supply from his dealer.

Mr. A’s total testosterone level, measured in the morning when it should be near its diurnal peak, was 127 ng/dl (normal range is 270 to 1,070 ng/dl). Physical examination revealed that his testicles had shrunk to the size of marbles (each approximately 5 mm in diameter). He was referred to an endocrinologist for evaluation and was simultaneously started on fluoxetine, 20 mg/d.

Table 2

LABORATORY ABNORMALITIES ASSOCIATED WITH ANABOLIC STEROID ABUSE

 

  • Elevated red blood cell count and hematocrit
  • Unfavorable lipid profile changes
  • Changes in LH, FSH, testosterone, and estradiol levels
  • Reduced sperm cell count
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

He returned 2 weeks later, exhibiting little improvement and wanting to resume steroids ‘because it was the only thing that really helped.’ Instead, he agreed to continue on fluoxetine and remain in follow-up. At 4 weeks, he noticed a decrease in panic attacks, return of normal mood, decreased anhedonia, and loss of suicidal ideation. He continued taking fluoxetine for another 3 months but then abruptly disappeared from treatment.

Mr. A resurfaced about 1 year later, revealing to the psychiatrist that he had taken yet another cycle of anabolic steroids, largely because he feared losing his muscle mass. His panic attacks had recurred almost immediately when he began tapering down from the peak of this cycle, and he agreed to resume taking fluoxetine.

 

 

A look at Mr. A’s extended history may provide clues to his persistent anabolic steroid abuse problem. He had displayed prominent symptoms of conduct disorder as a child. He had been truant from school, had occasionally run away from home, and had been involved in several misdemeanors. While in high school, he typically drank 10 to 12 beers over a weekend and had experimented with hallucinogenic mushrooms and 3,4-methylenedioxymethamphetamine (‘ecstasy’).

He started weightlifting while in high school and by age 17 was visiting the gym every day. He began college on a football scholarship but dropped out after 1 year. Starting in his early 20s, he competed in several bodybuilding contests.

Despite his impressive muscularity, Mr. A was anxious about his body appearance. He often would not take off his shirt—even when at the beach or a swimming pool—for fear that he would appear too small. He sometimes wore heavy sweatpants in the sweltering heat to conceal his legs. He also admitted spending as much as 2 hours a day examining himself in the mirror. ‘Sometimes when I get a bad (look at) myself, I will refuse to go out for the rest of the day,’ he said.

Mr. A has had a succession of girlfriends, but his rigid commitment to diet and exercise invariably ended these relationships.

At this point, would you first address Mr. A’s apparent substance use problem or the underlying body dysmorphic symptoms?

Dr. Carter’s and Pope’s observations

Two comorbidities noted here—substance abuse and body dysmorphic disorder—are common among anabolic steroid abusers. Addressing these problems, especially the body dysmorphic disorder, may sometimes help patients who are unwilling to address their steroid use directly. Body dysmorphic disorder may respond to selective serotonin reuptake inhibitors7 and cognitive-behavioral therapy.8

Anabolic steroids are not associated with immediate intoxicating effects, and ICD-10 categorizes them as substances not associated with dependence. After prolonged use at high doses, however, anabolic steroids are often associated with euphoria. Researchers also have found that some steroid abusers do meet DSM-IV criteria for substance dependence.6

Beyond the direct psychotropic effects of anabolic steroids, the depressive symptoms commonly seen during their withdrawal may perpetuate the dependence, as was the case with Mr. A. Most depressive symptoms that follow steroid cessation do not require drug therapy,3 but Mr. A developed severe and persistent depressive symptoms, complicated by panic disorder and body image concerns at a level diagnostic of body dysmorphic disorder. Such body image concerns often precipitate relapse into steroid use.

Conclusion: Another setback

As of this writing, Mr. A is again lost to follow-up. After taking fluoxetine and keeping monthly appointments for about 6 months, he failed to arrive for a visit and did not set another appointment. The patient may have once again stopped medication and embarked on yet another cycle of anabolic steroid use. If this is so, we can only hope that he returns to treatment before it is too late.

Related resources

Drug brand names

 

  • Fluoxetine • Prozac
  • Nandrolone decanoate • Deca-Durabolin
  • Oxymetholone • Anadrol
  • Stanozolol • Winstrol

Disclosure

Dr. Carter reports that he receives research/grant support from or is a consultant to Eli Lilly and Co., Pfizer Inc., and Ortho-McNeil Pharmaceutical.

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

References

 

1. Kouri E, Pope HG, Jr, Katz DL, Oliva P. Fat free mass index in users and non-users of anabolic-androgenic steroids. Clin J Sport Med 1995;5:223-8.

2. National Household Survey on Drug Abuse, 1994: http://www.icpsr.umich.edu.

3. Pope HG, Jr, Brower KJ. Anabolic-androgenic steroid abuse. In: Sadock BJ, Sadock VA (eds). Comprehensive textbook of psychiatry (7th ed). Philadelphia: Lippincott Williams & Wilkins, 2000;1085-95.

4. Buckley WA, Yesalis CE, 3rd, Friedl KE, et al. Estimated prevalence of anabolic steroid use among male high school seniors. JAMA 1988;260(23):3441-5.

5. Pope HG, Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. Arch Gen Psychiatry 1994;51:375-82.

6. Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

7. Phillips KA. Pharmacologic treatment of body dysmorphic disorder: A review of empirical data and a proposed treatment algorithm. Psychiatr Clin North Am 2000;7:59-82.

8. Rosen JC, Reiter J, Orosan P. Cognitive/behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol 1995;63:2639.-

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Initial visit: Road rage or ‘roid’ rage?

Mr. A, 25, was arrested after police interrupted an altercation between him and a senior citizen at a stoplight. He had emerged from his car, walked over to the older driver in front of him, ripped open the car door, and pulled the man out of the car and onto the street. He was still yelling at the victim when a passing officer intervened.

Mr. A was charged with assault. After a plea bargain, he was sentenced to probation and fined. He had been seeing his probation officer every 2 weeks, but his parents were worried about his erratic and sometimes defiant behavior and insisted he see a psychiatrist. He reluctantly agreed to one consultation, largely because his parents threatened to withhold financial support if he failed to do so.

The first thing the psychiatrist noticed was Mr. A’s striking muscular appearance. He was approximately 5 feet, 7 inches tall, weighed at least 200 pounds, and had a 30-inch waist and less than 10% body fat.

Dr. Carter’s and Pope’s observations

Mr. A’s diagnosis should be suspected immediately upon his entering the office. Extensive anabolic steroid use produces body changes that can be diagnosed almost at a glance. It is virtually impossible to achieve a level of muscle mass comparable to what Mr. A exhibited without the use of anabolic steroids.1

Remarkably, however, most people—including Mr. A’s parents, law enforcement personnel, and even some members of the treatment team—failed to diagnose Mr. A’s steroid use. He somehow convinced them that his extreme muscularity was the result of hard work, dedication, and scrupulous attention to diet. This suggests that steroid abuse cases involving serious violence—such as that of Mr. A—frequently go unreported and undiagnosed and are probably more common than we suspect.

Epidemiologic data suggest that clinicians should become familiar with the presentation of patients who are using anabolic steroids (Box).

Evaluation: ‘Stacking’ up

Mr. A at first vehemently denied that he had ever used anabolic steroids. After a more detailed conversation, during which the clinician demonstrated some knowledge of this area, Mr. A eventually conceded that he was taking a substantial weekly dose of the drugs at the time of the assault.

A subsequent clinical evaluation revealed that Mr. A had taken several ‘cycles’ (courses) of anabolic steroids over the last 2 to 3 years. Each cycle lasted 10 to 16 weeks and had been characterized by simultaneous use of two or more steroids, a practice known as ‘stacking.’

Mr. A started his first cycle with a modest ‘stack’ of drugs: testosterone cypionate, 200 mg twice a week, and stanozolol, 10 mg/d. Taken together, these dosages represented roughly 470 mg of testosterone equivalent per week—about 10 times the weekly secretion of testosterone in a normal male. He noticed no change in mood during this initial cycle.

With subsequent cycles, however, Mr. A became increasingly obsessed with his body image and used higher dosages. When the assault occurred, he was taking testosterone cypionate, 800 mg a week, nandrolone decanoate, 400 mg a week, and oxymetholone, 50 mg/d. With this regimen—the weekly equivalent of 1,550 mg of testosterone—Mr. A noticed prominent mood changes that met DSM-IV criteria for a manic episode. He experienced euphoria, dramatic irritability, limitless self-confidence, decreased need for sleep, distractibility, extreme recklessness (driving too fast, spending too freely), and some mildly paranoid ideation (without frank delusions). He admitted that he had twice assaulted his girlfriend and that he invariably became enraged at even the slightest annoyance when driving in traffic. He revealed that although the altercation with the older driver had led to his first arrest for ‘road rage,’ it was his third such incident.

The clinician warned Mr. A that continued steroid use could worsen his behavior—and lead to more serious trouble later on. Mr. A, however, said he was more afraid of losing muscle mass and becoming ‘small again.’ When the clinician mentioned that use of anabolic steroids without a prescription is illegal, Mr. A retorted that several of his friends had used the drugs without legal consequences.

Mr. A left the office showing no inclination to return for further treatment. The clinician could only offer to be available in the future.

Box

 

ANABOLIC STEROID ABUSE: BEYOND THE GYM

The National Household Survey on Drug Abuse, which last assessed anabolic steroid use in 1994, estimated that about 1 million Americans had used anabolic steroids at some point, with 30% of those reporting use within the previous year. Among subjects who reported use within the last 3 years, the ratio of males to females was about 13 to 1.2

Clearly, anabolic steroid abuse is no longer exclusive to professional football players and other elite male athletes. In fact, more people appear to be using anabolic steroids to improve their physiques, rather than to enhance athletic performance.3 Evidence points to increasing use by adolescents, with one survey reporting current or past use by 6.6% of male high school seniors.4

 

 

What medical sequelae await Mr. A if he continues to abuse steroids? How would you convince him to stay in treatment?

Dr. Carter’s and Pope’s observations

Mr. A’s path to mania has been well demonstrated in the literature. Hypomania or even frank manic syndromes, sometimes associated with violent behavior, are rare at weekly doses of 300 mg of testosterone equivalent. At weekly doses of >1,000 mg, psychiatric syndromes such as hypomania or mania may occur in almost one-half of cases.5

If he continues to abuse anabolic steroids, however, Mr. A could experience adverse physical reactions ranging from embarrassing acne and male-pattern baldness (Table 1) to rare and life-threatening hepatic effects such as cholestatic jaundice and peliosis hepatitis (blood-filled cysts in the liver).

Table 1

ANABOLIC STEROID ABUSE: COMMON PHYSICAL FINDINGS

 

  • Hypertrophic muscularity, disproportionately in upper torso
  • Acne on face, shoulders, and back
  • Male-pattern baldness
  • Testicular atrophy and gynecomastia in men
  • Clitoral enlargement, decreased breast size, hirsutism, and deepening of voice in women
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

The risk of atherosclerotic disease or prostate cancer later in life may also be greatly increased.

More common laboratory changes include:

 

  • increased red blood cell count, hemoglobin and hematocrit
  • elevated liver function readings (although these must not be confused with enzymes that originate from muscle tissue)
  • and unfavorable changes in triglycerides, total cholesterol, and HDL:LDL cholesterol ratios (Table 2).

Other potential laboratory changes with steroid abuse include decreased luteinizing hormone and follicle-stimulating hormone due to feedback inhibition. Feedback inhibition will also reduce testosterone and estradiol levels with use of anabolic steroids other than testosterone esters. These levels, however, would both be elevated with use of testosterone esters alone.

In men, testicular atrophy and decreased sperm count are generally reversible manifestations of steroid abuse, whereas gynecomastia may be irreversible and require surgical intervention in advanced cases.3,6 Women who use anabolic steroids (such as for body-building) are vulnerable to disrupted menstrual cycles, decreased breast size, and masculinizing effects including enlarged clitoris, hirsutism, and deepening of the voice.6

In adolescents, anabolic steroid use may cause premature closure of the epiphyses, leading to shortened stature.3

Unfortunately, warnings about these many adverse effects rarely deter anabolic steroid users such as Mr. A or persuade them to continue in treatment of any type. Most young anabolic steroid abusers report that they have never felt significant adverse effects from steroid use and know of no one who has experienced such effects. The dramatic muscle gains they have witnessed in themselves and in other users decisively outweigh what they perceive to be remote threats of adverse consequences.

Follow-up: Return to treatment

We didn’t hear from Mr. A until about 18 months later, when he unexpectedly requested a consultation.

Upon arrival, Mr. A exhibited major depression with prominent anhedonia, hypersomnia of 12 to 14 hours per night, loss of appetite, fatigue, prominent psychomotor retardation, feelings of guilt, difficulty concentrating, and suicidal thoughts (but without a frank plan). He also reported panic attacks that were randomly occurring each day, usually in public.

Mr. A conceded that he had experienced similar depressive episodes after stopping anabolic steroid use, but that they typically ran their course after 2 to 3 weeks. He said the present episode showed no sign of abating after nearly 2 months. He had attempted to ‘treat’ this episode by resuming anabolic steroid use, but he could not get an adequate supply from his dealer.

Mr. A’s total testosterone level, measured in the morning when it should be near its diurnal peak, was 127 ng/dl (normal range is 270 to 1,070 ng/dl). Physical examination revealed that his testicles had shrunk to the size of marbles (each approximately 5 mm in diameter). He was referred to an endocrinologist for evaluation and was simultaneously started on fluoxetine, 20 mg/d.

Table 2

LABORATORY ABNORMALITIES ASSOCIATED WITH ANABOLIC STEROID ABUSE

 

  • Elevated red blood cell count and hematocrit
  • Unfavorable lipid profile changes
  • Changes in LH, FSH, testosterone, and estradiol levels
  • Reduced sperm cell count
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

He returned 2 weeks later, exhibiting little improvement and wanting to resume steroids ‘because it was the only thing that really helped.’ Instead, he agreed to continue on fluoxetine and remain in follow-up. At 4 weeks, he noticed a decrease in panic attacks, return of normal mood, decreased anhedonia, and loss of suicidal ideation. He continued taking fluoxetine for another 3 months but then abruptly disappeared from treatment.

Mr. A resurfaced about 1 year later, revealing to the psychiatrist that he had taken yet another cycle of anabolic steroids, largely because he feared losing his muscle mass. His panic attacks had recurred almost immediately when he began tapering down from the peak of this cycle, and he agreed to resume taking fluoxetine.

 

 

A look at Mr. A’s extended history may provide clues to his persistent anabolic steroid abuse problem. He had displayed prominent symptoms of conduct disorder as a child. He had been truant from school, had occasionally run away from home, and had been involved in several misdemeanors. While in high school, he typically drank 10 to 12 beers over a weekend and had experimented with hallucinogenic mushrooms and 3,4-methylenedioxymethamphetamine (‘ecstasy’).

He started weightlifting while in high school and by age 17 was visiting the gym every day. He began college on a football scholarship but dropped out after 1 year. Starting in his early 20s, he competed in several bodybuilding contests.

Despite his impressive muscularity, Mr. A was anxious about his body appearance. He often would not take off his shirt—even when at the beach or a swimming pool—for fear that he would appear too small. He sometimes wore heavy sweatpants in the sweltering heat to conceal his legs. He also admitted spending as much as 2 hours a day examining himself in the mirror. ‘Sometimes when I get a bad (look at) myself, I will refuse to go out for the rest of the day,’ he said.

Mr. A has had a succession of girlfriends, but his rigid commitment to diet and exercise invariably ended these relationships.

At this point, would you first address Mr. A’s apparent substance use problem or the underlying body dysmorphic symptoms?

Dr. Carter’s and Pope’s observations

Two comorbidities noted here—substance abuse and body dysmorphic disorder—are common among anabolic steroid abusers. Addressing these problems, especially the body dysmorphic disorder, may sometimes help patients who are unwilling to address their steroid use directly. Body dysmorphic disorder may respond to selective serotonin reuptake inhibitors7 and cognitive-behavioral therapy.8

Anabolic steroids are not associated with immediate intoxicating effects, and ICD-10 categorizes them as substances not associated with dependence. After prolonged use at high doses, however, anabolic steroids are often associated with euphoria. Researchers also have found that some steroid abusers do meet DSM-IV criteria for substance dependence.6

Beyond the direct psychotropic effects of anabolic steroids, the depressive symptoms commonly seen during their withdrawal may perpetuate the dependence, as was the case with Mr. A. Most depressive symptoms that follow steroid cessation do not require drug therapy,3 but Mr. A developed severe and persistent depressive symptoms, complicated by panic disorder and body image concerns at a level diagnostic of body dysmorphic disorder. Such body image concerns often precipitate relapse into steroid use.

Conclusion: Another setback

As of this writing, Mr. A is again lost to follow-up. After taking fluoxetine and keeping monthly appointments for about 6 months, he failed to arrive for a visit and did not set another appointment. The patient may have once again stopped medication and embarked on yet another cycle of anabolic steroid use. If this is so, we can only hope that he returns to treatment before it is too late.

Related resources

Drug brand names

 

  • Fluoxetine • Prozac
  • Nandrolone decanoate • Deca-Durabolin
  • Oxymetholone • Anadrol
  • Stanozolol • Winstrol

Disclosure

Dr. Carter reports that he receives research/grant support from or is a consultant to Eli Lilly and Co., Pfizer Inc., and Ortho-McNeil Pharmaceutical.

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

Initial visit: Road rage or ‘roid’ rage?

Mr. A, 25, was arrested after police interrupted an altercation between him and a senior citizen at a stoplight. He had emerged from his car, walked over to the older driver in front of him, ripped open the car door, and pulled the man out of the car and onto the street. He was still yelling at the victim when a passing officer intervened.

Mr. A was charged with assault. After a plea bargain, he was sentenced to probation and fined. He had been seeing his probation officer every 2 weeks, but his parents were worried about his erratic and sometimes defiant behavior and insisted he see a psychiatrist. He reluctantly agreed to one consultation, largely because his parents threatened to withhold financial support if he failed to do so.

The first thing the psychiatrist noticed was Mr. A’s striking muscular appearance. He was approximately 5 feet, 7 inches tall, weighed at least 200 pounds, and had a 30-inch waist and less than 10% body fat.

Dr. Carter’s and Pope’s observations

Mr. A’s diagnosis should be suspected immediately upon his entering the office. Extensive anabolic steroid use produces body changes that can be diagnosed almost at a glance. It is virtually impossible to achieve a level of muscle mass comparable to what Mr. A exhibited without the use of anabolic steroids.1

Remarkably, however, most people—including Mr. A’s parents, law enforcement personnel, and even some members of the treatment team—failed to diagnose Mr. A’s steroid use. He somehow convinced them that his extreme muscularity was the result of hard work, dedication, and scrupulous attention to diet. This suggests that steroid abuse cases involving serious violence—such as that of Mr. A—frequently go unreported and undiagnosed and are probably more common than we suspect.

Epidemiologic data suggest that clinicians should become familiar with the presentation of patients who are using anabolic steroids (Box).

Evaluation: ‘Stacking’ up

Mr. A at first vehemently denied that he had ever used anabolic steroids. After a more detailed conversation, during which the clinician demonstrated some knowledge of this area, Mr. A eventually conceded that he was taking a substantial weekly dose of the drugs at the time of the assault.

A subsequent clinical evaluation revealed that Mr. A had taken several ‘cycles’ (courses) of anabolic steroids over the last 2 to 3 years. Each cycle lasted 10 to 16 weeks and had been characterized by simultaneous use of two or more steroids, a practice known as ‘stacking.’

Mr. A started his first cycle with a modest ‘stack’ of drugs: testosterone cypionate, 200 mg twice a week, and stanozolol, 10 mg/d. Taken together, these dosages represented roughly 470 mg of testosterone equivalent per week—about 10 times the weekly secretion of testosterone in a normal male. He noticed no change in mood during this initial cycle.

With subsequent cycles, however, Mr. A became increasingly obsessed with his body image and used higher dosages. When the assault occurred, he was taking testosterone cypionate, 800 mg a week, nandrolone decanoate, 400 mg a week, and oxymetholone, 50 mg/d. With this regimen—the weekly equivalent of 1,550 mg of testosterone—Mr. A noticed prominent mood changes that met DSM-IV criteria for a manic episode. He experienced euphoria, dramatic irritability, limitless self-confidence, decreased need for sleep, distractibility, extreme recklessness (driving too fast, spending too freely), and some mildly paranoid ideation (without frank delusions). He admitted that he had twice assaulted his girlfriend and that he invariably became enraged at even the slightest annoyance when driving in traffic. He revealed that although the altercation with the older driver had led to his first arrest for ‘road rage,’ it was his third such incident.

The clinician warned Mr. A that continued steroid use could worsen his behavior—and lead to more serious trouble later on. Mr. A, however, said he was more afraid of losing muscle mass and becoming ‘small again.’ When the clinician mentioned that use of anabolic steroids without a prescription is illegal, Mr. A retorted that several of his friends had used the drugs without legal consequences.

Mr. A left the office showing no inclination to return for further treatment. The clinician could only offer to be available in the future.

Box

 

ANABOLIC STEROID ABUSE: BEYOND THE GYM

The National Household Survey on Drug Abuse, which last assessed anabolic steroid use in 1994, estimated that about 1 million Americans had used anabolic steroids at some point, with 30% of those reporting use within the previous year. Among subjects who reported use within the last 3 years, the ratio of males to females was about 13 to 1.2

Clearly, anabolic steroid abuse is no longer exclusive to professional football players and other elite male athletes. In fact, more people appear to be using anabolic steroids to improve their physiques, rather than to enhance athletic performance.3 Evidence points to increasing use by adolescents, with one survey reporting current or past use by 6.6% of male high school seniors.4

 

 

What medical sequelae await Mr. A if he continues to abuse steroids? How would you convince him to stay in treatment?

Dr. Carter’s and Pope’s observations

Mr. A’s path to mania has been well demonstrated in the literature. Hypomania or even frank manic syndromes, sometimes associated with violent behavior, are rare at weekly doses of 300 mg of testosterone equivalent. At weekly doses of >1,000 mg, psychiatric syndromes such as hypomania or mania may occur in almost one-half of cases.5

If he continues to abuse anabolic steroids, however, Mr. A could experience adverse physical reactions ranging from embarrassing acne and male-pattern baldness (Table 1) to rare and life-threatening hepatic effects such as cholestatic jaundice and peliosis hepatitis (blood-filled cysts in the liver).

Table 1

ANABOLIC STEROID ABUSE: COMMON PHYSICAL FINDINGS

 

  • Hypertrophic muscularity, disproportionately in upper torso
  • Acne on face, shoulders, and back
  • Male-pattern baldness
  • Testicular atrophy and gynecomastia in men
  • Clitoral enlargement, decreased breast size, hirsutism, and deepening of voice in women
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

The risk of atherosclerotic disease or prostate cancer later in life may also be greatly increased.

More common laboratory changes include:

 

  • increased red blood cell count, hemoglobin and hematocrit
  • elevated liver function readings (although these must not be confused with enzymes that originate from muscle tissue)
  • and unfavorable changes in triglycerides, total cholesterol, and HDL:LDL cholesterol ratios (Table 2).

Other potential laboratory changes with steroid abuse include decreased luteinizing hormone and follicle-stimulating hormone due to feedback inhibition. Feedback inhibition will also reduce testosterone and estradiol levels with use of anabolic steroids other than testosterone esters. These levels, however, would both be elevated with use of testosterone esters alone.

In men, testicular atrophy and decreased sperm count are generally reversible manifestations of steroid abuse, whereas gynecomastia may be irreversible and require surgical intervention in advanced cases.3,6 Women who use anabolic steroids (such as for body-building) are vulnerable to disrupted menstrual cycles, decreased breast size, and masculinizing effects including enlarged clitoris, hirsutism, and deepening of the voice.6

In adolescents, anabolic steroid use may cause premature closure of the epiphyses, leading to shortened stature.3

Unfortunately, warnings about these many adverse effects rarely deter anabolic steroid users such as Mr. A or persuade them to continue in treatment of any type. Most young anabolic steroid abusers report that they have never felt significant adverse effects from steroid use and know of no one who has experienced such effects. The dramatic muscle gains they have witnessed in themselves and in other users decisively outweigh what they perceive to be remote threats of adverse consequences.

Follow-up: Return to treatment

We didn’t hear from Mr. A until about 18 months later, when he unexpectedly requested a consultation.

Upon arrival, Mr. A exhibited major depression with prominent anhedonia, hypersomnia of 12 to 14 hours per night, loss of appetite, fatigue, prominent psychomotor retardation, feelings of guilt, difficulty concentrating, and suicidal thoughts (but without a frank plan). He also reported panic attacks that were randomly occurring each day, usually in public.

Mr. A conceded that he had experienced similar depressive episodes after stopping anabolic steroid use, but that they typically ran their course after 2 to 3 weeks. He said the present episode showed no sign of abating after nearly 2 months. He had attempted to ‘treat’ this episode by resuming anabolic steroid use, but he could not get an adequate supply from his dealer.

Mr. A’s total testosterone level, measured in the morning when it should be near its diurnal peak, was 127 ng/dl (normal range is 270 to 1,070 ng/dl). Physical examination revealed that his testicles had shrunk to the size of marbles (each approximately 5 mm in diameter). He was referred to an endocrinologist for evaluation and was simultaneously started on fluoxetine, 20 mg/d.

Table 2

LABORATORY ABNORMALITIES ASSOCIATED WITH ANABOLIC STEROID ABUSE

 

  • Elevated red blood cell count and hematocrit
  • Unfavorable lipid profile changes
  • Changes in LH, FSH, testosterone, and estradiol levels
  • Reduced sperm cell count
Source: Adapted from Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

He returned 2 weeks later, exhibiting little improvement and wanting to resume steroids ‘because it was the only thing that really helped.’ Instead, he agreed to continue on fluoxetine and remain in follow-up. At 4 weeks, he noticed a decrease in panic attacks, return of normal mood, decreased anhedonia, and loss of suicidal ideation. He continued taking fluoxetine for another 3 months but then abruptly disappeared from treatment.

Mr. A resurfaced about 1 year later, revealing to the psychiatrist that he had taken yet another cycle of anabolic steroids, largely because he feared losing his muscle mass. His panic attacks had recurred almost immediately when he began tapering down from the peak of this cycle, and he agreed to resume taking fluoxetine.

 

 

A look at Mr. A’s extended history may provide clues to his persistent anabolic steroid abuse problem. He had displayed prominent symptoms of conduct disorder as a child. He had been truant from school, had occasionally run away from home, and had been involved in several misdemeanors. While in high school, he typically drank 10 to 12 beers over a weekend and had experimented with hallucinogenic mushrooms and 3,4-methylenedioxymethamphetamine (‘ecstasy’).

He started weightlifting while in high school and by age 17 was visiting the gym every day. He began college on a football scholarship but dropped out after 1 year. Starting in his early 20s, he competed in several bodybuilding contests.

Despite his impressive muscularity, Mr. A was anxious about his body appearance. He often would not take off his shirt—even when at the beach or a swimming pool—for fear that he would appear too small. He sometimes wore heavy sweatpants in the sweltering heat to conceal his legs. He also admitted spending as much as 2 hours a day examining himself in the mirror. ‘Sometimes when I get a bad (look at) myself, I will refuse to go out for the rest of the day,’ he said.

Mr. A has had a succession of girlfriends, but his rigid commitment to diet and exercise invariably ended these relationships.

At this point, would you first address Mr. A’s apparent substance use problem or the underlying body dysmorphic symptoms?

Dr. Carter’s and Pope’s observations

Two comorbidities noted here—substance abuse and body dysmorphic disorder—are common among anabolic steroid abusers. Addressing these problems, especially the body dysmorphic disorder, may sometimes help patients who are unwilling to address their steroid use directly. Body dysmorphic disorder may respond to selective serotonin reuptake inhibitors7 and cognitive-behavioral therapy.8

Anabolic steroids are not associated with immediate intoxicating effects, and ICD-10 categorizes them as substances not associated with dependence. After prolonged use at high doses, however, anabolic steroids are often associated with euphoria. Researchers also have found that some steroid abusers do meet DSM-IV criteria for substance dependence.6

Beyond the direct psychotropic effects of anabolic steroids, the depressive symptoms commonly seen during their withdrawal may perpetuate the dependence, as was the case with Mr. A. Most depressive symptoms that follow steroid cessation do not require drug therapy,3 but Mr. A developed severe and persistent depressive symptoms, complicated by panic disorder and body image concerns at a level diagnostic of body dysmorphic disorder. Such body image concerns often precipitate relapse into steroid use.

Conclusion: Another setback

As of this writing, Mr. A is again lost to follow-up. After taking fluoxetine and keeping monthly appointments for about 6 months, he failed to arrive for a visit and did not set another appointment. The patient may have once again stopped medication and embarked on yet another cycle of anabolic steroid use. If this is so, we can only hope that he returns to treatment before it is too late.

Related resources

Drug brand names

 

  • Fluoxetine • Prozac
  • Nandrolone decanoate • Deca-Durabolin
  • Oxymetholone • Anadrol
  • Stanozolol • Winstrol

Disclosure

Dr. Carter reports that he receives research/grant support from or is a consultant to Eli Lilly and Co., Pfizer Inc., and Ortho-McNeil Pharmaceutical.

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

References

 

1. Kouri E, Pope HG, Jr, Katz DL, Oliva P. Fat free mass index in users and non-users of anabolic-androgenic steroids. Clin J Sport Med 1995;5:223-8.

2. National Household Survey on Drug Abuse, 1994: http://www.icpsr.umich.edu.

3. Pope HG, Jr, Brower KJ. Anabolic-androgenic steroid abuse. In: Sadock BJ, Sadock VA (eds). Comprehensive textbook of psychiatry (7th ed). Philadelphia: Lippincott Williams & Wilkins, 2000;1085-95.

4. Buckley WA, Yesalis CE, 3rd, Friedl KE, et al. Estimated prevalence of anabolic steroid use among male high school seniors. JAMA 1988;260(23):3441-5.

5. Pope HG, Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. Arch Gen Psychiatry 1994;51:375-82.

6. Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

7. Phillips KA. Pharmacologic treatment of body dysmorphic disorder: A review of empirical data and a proposed treatment algorithm. Psychiatr Clin North Am 2000;7:59-82.

8. Rosen JC, Reiter J, Orosan P. Cognitive/behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol 1995;63:2639.-

References

 

1. Kouri E, Pope HG, Jr, Katz DL, Oliva P. Fat free mass index in users and non-users of anabolic-androgenic steroids. Clin J Sport Med 1995;5:223-8.

2. National Household Survey on Drug Abuse, 1994: http://www.icpsr.umich.edu.

3. Pope HG, Jr, Brower KJ. Anabolic-androgenic steroid abuse. In: Sadock BJ, Sadock VA (eds). Comprehensive textbook of psychiatry (7th ed). Philadelphia: Lippincott Williams & Wilkins, 2000;1085-95.

4. Buckley WA, Yesalis CE, 3rd, Friedl KE, et al. Estimated prevalence of anabolic steroid use among male high school seniors. JAMA 1988;260(23):3441-5.

5. Pope HG, Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. Arch Gen Psychiatry 1994;51:375-82.

6. Brower KJ. Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002;4:377-83.

7. Phillips KA. Pharmacologic treatment of body dysmorphic disorder: A review of empirical data and a proposed treatment algorithm. Psychiatr Clin North Am 2000;7:59-82.

8. Rosen JC, Reiter J, Orosan P. Cognitive/behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol 1995;63:2639.-

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At age 44 and physically fit, he feared imminent death

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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

Overlap of DSM-IV criteria for major depression and generalized anxiety disorder

 Major depressionGeneralized anxiety disorder
MoodDepression, irritabilityAnxiety, worry, irritability
PsychomotorAgitationRestlessness, keyed-up/on-edge feeling
EnergyFatigue or loss of energyEasily fatigued
ConcentrationDiminished abilityDifficulty
SleepDecreased or increasedDecreased or restless/unsatisfying
 

 

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

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.

References

1. Kessler RC, Keller MB, Wittchen HU. The epidemiology of generalized anxiety disorder. Psychiatr Clin North Am 2001;24:19-39.

2. Kessler RC, DuPont RL, Berglund P, Wittchen HU. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. AmJPsychiatry 1999;156:1915-23.

3. Olfson M. Barriers to the effective treatment of anxiety disorders. Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

4. Sheehan DV. Should generalized anxiety disorder be treated long term? Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

5. Lin EH, Von Korff M, Katon W, Bush T, Simon GE, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care. 1995;33(1):67-74.

6. Sheehan DV. Should generalized anxiety disorder be treated long term? Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

7. Davidson JR, DuPont RL, Hedges D, Haskins JT. Efficacy, safety, tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999;60:528-35.

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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

Overlap of DSM-IV criteria for major depression and generalized anxiety disorder

 Major depressionGeneralized anxiety disorder
MoodDepression, irritabilityAnxiety, worry, irritability
PsychomotorAgitationRestlessness, keyed-up/on-edge feeling
EnergyFatigue or loss of energyEasily fatigued
ConcentrationDiminished abilityDifficulty
SleepDecreased or increasedDecreased or restless/unsatisfying
 

 

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

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

Overlap of DSM-IV criteria for major depression and generalized anxiety disorder

 Major depressionGeneralized anxiety disorder
MoodDepression, irritabilityAnxiety, worry, irritability
PsychomotorAgitationRestlessness, keyed-up/on-edge feeling
EnergyFatigue or loss of energyEasily fatigued
ConcentrationDiminished abilityDifficulty
SleepDecreased or increasedDecreased or restless/unsatisfying
 

 

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

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.

References

1. Kessler RC, Keller MB, Wittchen HU. The epidemiology of generalized anxiety disorder. Psychiatr Clin North Am 2001;24:19-39.

2. Kessler RC, DuPont RL, Berglund P, Wittchen HU. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. AmJPsychiatry 1999;156:1915-23.

3. Olfson M. Barriers to the effective treatment of anxiety disorders. Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

4. Sheehan DV. Should generalized anxiety disorder be treated long term? Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

5. Lin EH, Von Korff M, Katon W, Bush T, Simon GE, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care. 1995;33(1):67-74.

6. Sheehan DV. Should generalized anxiety disorder be treated long term? Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

7. Davidson JR, DuPont RL, Hedges D, Haskins JT. Efficacy, safety, tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999;60:528-35.

References

1. Kessler RC, Keller MB, Wittchen HU. The epidemiology of generalized anxiety disorder. Psychiatr Clin North Am 2001;24:19-39.

2. Kessler RC, DuPont RL, Berglund P, Wittchen HU. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. AmJPsychiatry 1999;156:1915-23.

3. Olfson M. Barriers to the effective treatment of anxiety disorders. Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

4. Sheehan DV. Should generalized anxiety disorder be treated long term? Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

5. Lin EH, Von Korff M, Katon W, Bush T, Simon GE, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care. 1995;33(1):67-74.

6. Sheehan DV. Should generalized anxiety disorder be treated long term? Critical questions in anxiety disorders. Presented at the 2001 American Psychiatric Association Annual Meeting; New Orleans, LA.

7. Davidson JR, DuPont RL, Hedges D, Haskins JT. Efficacy, safety, tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999;60:528-35.

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