Appetite suppression and insomnia—both common, dose-related side effects of psychostimulants—can jeopardize treatment adherence for patients with attention-deficit/hyperactivity disorder (ADHD). The following strategies can minimize these effects.

First, wait and see

For most patients, the optimal psychostimulant dosage produces few or no side effects. Those that occur are usually minor, transient, and disappear as patients develop tolerance within days of starting medication.

The two most commonly used stimulants—methylphenidate and amphetamine—cause similar side effects.¹ No evidence suggests either is more effective or less tolerable than the other.

Fine-tune psychostimulants to the lowest dosage that produces maximum benefit and minimum side effects. If side effects persist beyond 7 to 10 days, the dosage is probably too high or the patient is taking another stimulating medication. Before you attribute insomnia or appetite suppression to psychostimulants, ask the patient if he or she is using a decongestant, caffeine, diet pills, systemic corticosteroids, systemic albuterol, or theophylline.

Countering appetite suppression

Approximately one-third of adult and pediatric ADHD patients report appetite suppression at therapeutic psychostimulant dosages, but in most patients this effect is transient or clinically insignificant. If a child taking psychostimulants is not eating or gaining weight appropriately:

• suggest that parents plan mealtimes before the patient’s next dose or give high-calorie snacks throughout the day. (This strategy, although recommended by the American Academy of Pediatrics, can be cumbersome and has limited long-term efficacy.)
• switch from amphetamine to methylphenidate or vice versa.
• add the antihistamine cyproheptadine, 4 mg, with morning and evening meals
• add mirtazapine, one-half of a 15-mg tablet at bedtime to stimulate appetite and initiate sleep.

If none of these interventions work, recommend drug holidays from ADHD medications as a last resort when impairment is lowest, such as during weekends, holidays, or summers.

Curbing insomnia

About 20% of prepubertal children and 75% to 80% of adults have difficulty falling asleep while taking ADHD medications.² For many patients it is not the medications but the mental and physical restlessness of ADHD that disturbs sleep. Take a careful baseline sleep history before starting psychostimulants to help you determine later if they are causing insomnia.

Avoid benzodiazepines, which may promote tolerance and dependence. I discourage using any hypnotic to treat insomnia that occurs as a side effect. Also avoid antihistamines (Benedryl, trazodone) that may leave the patient sedated the next day.

Try a trial nap. After fine-tuning the psychostimulant to the lowest optimal dosage, ask the patient to test his ability to sleep while on that dose by taking an afternoon nap. Most patients discover they can sleep well, proving to both patient and doctor that ADHD medications usually help sleep initiation or are sleep-neutral. A successful nap can ease a patient’s fear that her medication will keep her awake.

Even the longest extended-release psychostimulant formulations do not last the 14 to 16 hours of a typical waking day. This no-risk trial nap reassures patients that they can take supplemental doses as prescribed to assist them through even the longest workdays, without fear of sleep disruption.

Time-release formulations smooth the abrupt kinetics and rebound activation seen with immediate-release psychostimulants. But for patients taking immediate-release formulations, reducing the day’s last dose or taking the last dose earlier can often prevent medication-associated insomnia.

If insomnia persists, try:

• melatonin, 0.5 to 1.0 mg, at bedtime, 1 hour before bedtime, at sunset, or 6 hours before anticipated bedtime. I try to mimic the natural release of melatonin triggered by sunset, but no definitive data prove the most effective dosing time.
• alpha agonists such as clonidine, 0.1 to 0.2 mg at bedtime, or guanfacine, 1 to 2 mg at bedtime. These agents have proven efficacy for treating hyperactivity and sleep disturbances without causing tolerance but may be associated with nightmares in some children.³
• mirtazapine, one-half of a 15-mg tablet at bedtime.

Appetite suppression and insomnia—both common, dose-related side effects of psychostimulants—can jeopardize treatment adherence for patients with attention-deficit/hyperactivity disorder (ADHD). The following strategies can minimize these effects.

First, wait and see

For most patients, the optimal psychostimulant dosage produces few or no side effects. Those that occur are usually minor, transient, and disappear as patients develop tolerance within days of starting medication.

The two most commonly used stimulants—methylphenidate and amphetamine—cause similar side effects.¹ No evidence suggests either is more effective or less tolerable than the other.

Fine-tune psychostimulants to the lowest dosage that produces maximum benefit and minimum side effects. If side effects persist beyond 7 to 10 days, the dosage is probably too high or the patient is taking another stimulating medication. Before you attribute insomnia or appetite suppression to psychostimulants, ask the patient if he or she is using a decongestant, caffeine, diet pills, systemic corticosteroids, systemic albuterol, or theophylline.

Countering appetite suppression

Approximately one-third of adult and pediatric ADHD patients report appetite suppression at therapeutic psychostimulant dosages, but in most patients this effect is transient or clinically insignificant. If a child taking psychostimulants is not eating or gaining weight appropriately:

• suggest that parents plan mealtimes before the patient’s next dose or give high-calorie snacks throughout the day. (This strategy, although recommended by the American Academy of Pediatrics, can be cumbersome and has limited long-term efficacy.)
• switch from amphetamine to methylphenidate or vice versa.
• add the antihistamine cyproheptadine, 4 mg, with morning and evening meals
• add mirtazapine, one-half of a 15-mg tablet at bedtime to stimulate appetite and initiate sleep.

If none of these interventions work, recommend drug holidays from ADHD medications as a last resort when impairment is lowest, such as during weekends, holidays, or summers.

Curbing insomnia

About 20% of prepubertal children and 75% to 80% of adults have difficulty falling asleep while taking ADHD medications.² For many patients it is not the medications but the mental and physical restlessness of ADHD that disturbs sleep. Take a careful baseline sleep history before starting psychostimulants to help you determine later if they are causing insomnia.

Avoid benzodiazepines, which may promote tolerance and dependence. I discourage using any hypnotic to treat insomnia that occurs as a side effect. Also avoid antihistamines (Benedryl, trazodone) that may leave the patient sedated the next day.

Try a trial nap. After fine-tuning the psychostimulant to the lowest optimal dosage, ask the patient to test his ability to sleep while on that dose by taking an afternoon nap. Most patients discover they can sleep well, proving to both patient and doctor that ADHD medications usually help sleep initiation or are sleep-neutral. A successful nap can ease a patient’s fear that her medication will keep her awake.

Even the longest extended-release psychostimulant formulations do not last the 14 to 16 hours of a typical waking day. This no-risk trial nap reassures patients that they can take supplemental doses as prescribed to assist them through even the longest workdays, without fear of sleep disruption.

Time-release formulations smooth the abrupt kinetics and rebound activation seen with immediate-release psychostimulants. But for patients taking immediate-release formulations, reducing the day’s last dose or taking the last dose earlier can often prevent medication-associated insomnia.

If insomnia persists, try:

• melatonin, 0.5 to 1.0 mg, at bedtime, 1 hour before bedtime, at sunset, or 6 hours before anticipated bedtime. I try to mimic the natural release of melatonin triggered by sunset, but no definitive data prove the most effective dosing time.
• alpha agonists such as clonidine, 0.1 to 0.2 mg at bedtime, or guanfacine, 1 to 2 mg at bedtime. These agents have proven efficacy for treating hyperactivity and sleep disturbances without causing tolerance but may be associated with nightmares in some children.³
• mirtazapine, one-half of a 15-mg tablet at bedtime.

Appetite suppression and insomnia—both common, dose-related side effects of psychostimulants—can jeopardize treatment adherence for patients with attention-deficit/hyperactivity disorder (ADHD). The following strategies can minimize these effects.

First, wait and see

For most patients, the optimal psychostimulant dosage produces few or no side effects. Those that occur are usually minor, transient, and disappear as patients develop tolerance within days of starting medication.

The two most commonly used stimulants—methylphenidate and amphetamine—cause similar side effects.¹ No evidence suggests either is more effective or less tolerable than the other.

Fine-tune psychostimulants to the lowest dosage that produces maximum benefit and minimum side effects. If side effects persist beyond 7 to 10 days, the dosage is probably too high or the patient is taking another stimulating medication. Before you attribute insomnia or appetite suppression to psychostimulants, ask the patient if he or she is using a decongestant, caffeine, diet pills, systemic corticosteroids, systemic albuterol, or theophylline.

Countering appetite suppression

Approximately one-third of adult and pediatric ADHD patients report appetite suppression at therapeutic psychostimulant dosages, but in most patients this effect is transient or clinically insignificant. If a child taking psychostimulants is not eating or gaining weight appropriately:

• suggest that parents plan mealtimes before the patient’s next dose or give high-calorie snacks throughout the day. (This strategy, although recommended by the American Academy of Pediatrics, can be cumbersome and has limited long-term efficacy.)
• switch from amphetamine to methylphenidate or vice versa.
• add the antihistamine cyproheptadine, 4 mg, with morning and evening meals
• add mirtazapine, one-half of a 15-mg tablet at bedtime to stimulate appetite and initiate sleep.

If none of these interventions work, recommend drug holidays from ADHD medications as a last resort when impairment is lowest, such as during weekends, holidays, or summers.

Curbing insomnia

About 20% of prepubertal children and 75% to 80% of adults have difficulty falling asleep while taking ADHD medications.² For many patients it is not the medications but the mental and physical restlessness of ADHD that disturbs sleep. Take a careful baseline sleep history before starting psychostimulants to help you determine later if they are causing insomnia.

Avoid benzodiazepines, which may promote tolerance and dependence. I discourage using any hypnotic to treat insomnia that occurs as a side effect. Also avoid antihistamines (Benedryl, trazodone) that may leave the patient sedated the next day.

Try a trial nap. After fine-tuning the psychostimulant to the lowest optimal dosage, ask the patient to test his ability to sleep while on that dose by taking an afternoon nap. Most patients discover they can sleep well, proving to both patient and doctor that ADHD medications usually help sleep initiation or are sleep-neutral. A successful nap can ease a patient’s fear that her medication will keep her awake.

Even the longest extended-release psychostimulant formulations do not last the 14 to 16 hours of a typical waking day. This no-risk trial nap reassures patients that they can take supplemental doses as prescribed to assist them through even the longest workdays, without fear of sleep disruption.

Time-release formulations smooth the abrupt kinetics and rebound activation seen with immediate-release psychostimulants. But for patients taking immediate-release formulations, reducing the day’s last dose or taking the last dose earlier can often prevent medication-associated insomnia.

If insomnia persists, try:

• melatonin, 0.5 to 1.0 mg, at bedtime, 1 hour before bedtime, at sunset, or 6 hours before anticipated bedtime. I try to mimic the natural release of melatonin triggered by sunset, but no definitive data prove the most effective dosing time.
• alpha agonists such as clonidine, 0.1 to 0.2 mg at bedtime, or guanfacine, 1 to 2 mg at bedtime. These agents have proven efficacy for treating hyperactivity and sleep disturbances without causing tolerance but may be associated with nightmares in some children.³
• mirtazapine, one-half of a 15-mg tablet at bedtime.

Worker claims therapist disclosed confidential information

Cook County (IL) Circuit Court

A public works employee in Illinois received psychotherapy through his city’s wellness program. After the man left his position, he claimed in court that the treating therapist met with his former co-workers, disclosed his receipt of therapy to them, and told them he was unstable and capable of harming himself or others. The former employee argued that the disclosures violated Illinois law, caused him emotional distress, and made him unable to trust mental health professionals.

The defense denied that the therapist had violated the law or had made any disclosures. Instead, the defense argued that the co-workers—not the therapist—had voiced concern about the plaintiff. The defense maintained that the co-workers were confused about who had discussed the plaintiff, and that the therapist had not discussed him.

• The jury found for the defense.
  

Dr. Grant’s observations

The courts have recognized and protected the fundamental importance of confidentiality in the therapist/patient relationship.^{How to avoid ‘foreseeable’ harm,” Current Psychiatry, March 2005, at www.currentpsychiatry.com).}

Here, the request for consultation might suggest that an honest error in judgment occurred—the psychiatrist was simply puzzled by the patient’s medical symptoms. Although several doctors failed to diagnose NMS, shouldn’t the psychiatrists have been able to diagnose it?

NMS is a side-effect risk of atypical and conventional neuroleptics,^{Pearls: Identifying NMS with FEVER,”).}

The psychiatrists in this case did not conform to the standard of care, and consulting with another doctor did not absolve them of liability.

Worker claims therapist disclosed confidential information

Cook County (IL) Circuit Court

A public works employee in Illinois received psychotherapy through his city’s wellness program. After the man left his position, he claimed in court that the treating therapist met with his former co-workers, disclosed his receipt of therapy to them, and told them he was unstable and capable of harming himself or others. The former employee argued that the disclosures violated Illinois law, caused him emotional distress, and made him unable to trust mental health professionals.

The defense denied that the therapist had violated the law or had made any disclosures. Instead, the defense argued that the co-workers—not the therapist—had voiced concern about the plaintiff. The defense maintained that the co-workers were confused about who had discussed the plaintiff, and that the therapist had not discussed him.

• The jury found for the defense.
  

Dr. Grant’s observations

The courts have recognized and protected the fundamental importance of confidentiality in the therapist/patient relationship.^{How to avoid ‘foreseeable’ harm,” Current Psychiatry, March 2005, at www.currentpsychiatry.com).}

Here, the request for consultation might suggest that an honest error in judgment occurred—the psychiatrist was simply puzzled by the patient’s medical symptoms. Although several doctors failed to diagnose NMS, shouldn’t the psychiatrists have been able to diagnose it?

NMS is a side-effect risk of atypical and conventional neuroleptics,^{Pearls: Identifying NMS with FEVER,”).}

The psychiatrists in this case did not conform to the standard of care, and consulting with another doctor did not absolve them of liability.

Worker claims therapist disclosed confidential information

Cook County (IL) Circuit Court

A public works employee in Illinois received psychotherapy through his city’s wellness program. After the man left his position, he claimed in court that the treating therapist met with his former co-workers, disclosed his receipt of therapy to them, and told them he was unstable and capable of harming himself or others. The former employee argued that the disclosures violated Illinois law, caused him emotional distress, and made him unable to trust mental health professionals.

The defense denied that the therapist had violated the law or had made any disclosures. Instead, the defense argued that the co-workers—not the therapist—had voiced concern about the plaintiff. The defense maintained that the co-workers were confused about who had discussed the plaintiff, and that the therapist had not discussed him.

• The jury found for the defense.
  

Dr. Grant’s observations

The courts have recognized and protected the fundamental importance of confidentiality in the therapist/patient relationship.^{How to avoid ‘foreseeable’ harm,” Current Psychiatry, March 2005, at www.currentpsychiatry.com).}

Here, the request for consultation might suggest that an honest error in judgment occurred—the psychiatrist was simply puzzled by the patient’s medical symptoms. Although several doctors failed to diagnose NMS, shouldn’t the psychiatrists have been able to diagnose it?

NMS is a side-effect risk of atypical and conventional neuroleptics,^{Pearls: Identifying NMS with FEVER,”).}

The psychiatrists in this case did not conform to the standard of care, and consulting with another doctor did not absolve them of liability.

“What’s the best treatment for comorbid ADHD/bipolar mania?” by Drs. Nick C. Patel and Floyd R. Sallee (Current Psychiatry, April 2005) was well-written and offers excellent treatment guidelines. However, the idea that patients can have comorbid bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) is a fallacy.

I challenge any colleague, from the leading expert to the most recent graduate, to present a bona fide case of “comorbid” ADHD/bipolar disorder. I can prove that only one diagnosis is correct because:

• Bipolar disorder is more heritable than other psychiatric illnesses. Many patients labeled as having “comorbid” bipolar disorder and ADHD have parents with bipolar disorder or schizophrenia or are in foster care and their biological parents’ histories are unknown.
• I’ve seen hundreds of patients enter full-blown psychosis after another clinician put them on amphetamines or antidepressants while being treated for ADHD.
• Bipolar disorder can explain any so-called ADHD symptom.
• ADHD does not include moodiness or predatory aggression.

Over 10 years, I have diagnosed three or four patients as having comorbid bipolar disorder and ADHD. After a few years and inpatient treatments, these patients proved the second diagnosis wrong. We can decrease costs and avoid patients’ suffering by refining diagnostic criteria.

Manuel Mota-Castillo, MD, medical director
The Grove Academy, Sanford, FL
and Lake Mary Psychiatric Services
Lake Mary, FL

Drs. Patel and Sallee respond

Dr. Mota-Castillo’s argument is most often stated from the opposite point of view that bipolar symptoms, particularly in patients age <10, are almost indistinguishable from those of ADHD. Our article did not—and cannot—address this controversy.

Because the evidence has been inconclusive, it is unclear if comorbid bipolar disorder and ADHD result from overlapping DSM-IV-TR diagnostic criteria, or whether two concurrent disorders exist. Suffice it to say that ADHD and bipolar disorder have many phenotypes and are both highly—but distinctly—heritable.

Overlapping symptoms may confound clinical diagnosis and result in “false positives” but may not account for most bipolar youths with comorbid ADHD. In one study,¹ 56% of subjects with both disorders maintained a bipolar disorder diagnosis when overlapping ADHD symptoms were subtracted.

Combination pharmacotherapy is needed because mood stabilizers do not treat attention and neurocognitive problems associated with ADHD. Therefore, a psychostimulant trial may help euthymic bipolar children and adolescents. In a recent placebo-controlled study by Scheffer et al,² ADHD symptoms—as measured with the Clinical Global Impression of Improvement scale and based upon Conners’ Teachers and Parent Ratings—significantly improved among divalproex sodium responders receiving mixed amphetamine salts.

Dr. Mota-Castillo, however, brings up two important questions:

• Are childhood symptoms that result in ADHD diagnosis a prodromal manifestation of bipolar disorder in some patients? Data from the first 1,000 STEP-BD participants suggest that ADHD may be part of the developmental phenotype of bipolar disorder comorbidity. Participants with mood symptom onset before age 13 had higher rates of comorbid ADHD than did those whose mood symptoms surfaced later on.³
• Do psychostimulants hasten mood disorder onset in a child diagnosed with ADHD who has a high familial risk of a mood disorder? How these agents influence the course of bipolar disorder is unclear. DelBello et al⁴ reported that psychostimulant exposure may be a stressor in youths at risk for bipolar disorder, may progressively worsen affective symptoms over time, and may lead to earlier mood symptom onset.

Both questions need further exploration as the implications for clinical practice may be tremendous.

Results from numerous independent studies consistently suggest that patients can be diagnosed with comorbid bipolar disorder and ADHD. More research is needed, however, to solve this diagnostic conundrum.

Nick C. Patel, PharmD, PhD
Assistant professor
Departments of pharmacy practice and psychiatry
Floyd R. Sallee, MD, PhD
Professor, department of psychiatry
University of Cincinnati

“What’s the best treatment for comorbid ADHD/bipolar mania?” by Drs. Nick C. Patel and Floyd R. Sallee (Current Psychiatry, April 2005) was well-written and offers excellent treatment guidelines. However, the idea that patients can have comorbid bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) is a fallacy.

I challenge any colleague, from the leading expert to the most recent graduate, to present a bona fide case of “comorbid” ADHD/bipolar disorder. I can prove that only one diagnosis is correct because:

• Bipolar disorder is more heritable than other psychiatric illnesses. Many patients labeled as having “comorbid” bipolar disorder and ADHD have parents with bipolar disorder or schizophrenia or are in foster care and their biological parents’ histories are unknown.
• I’ve seen hundreds of patients enter full-blown psychosis after another clinician put them on amphetamines or antidepressants while being treated for ADHD.
• Bipolar disorder can explain any so-called ADHD symptom.
• ADHD does not include moodiness or predatory aggression.

Over 10 years, I have diagnosed three or four patients as having comorbid bipolar disorder and ADHD. After a few years and inpatient treatments, these patients proved the second diagnosis wrong. We can decrease costs and avoid patients’ suffering by refining diagnostic criteria.

Manuel Mota-Castillo, MD, medical director
The Grove Academy, Sanford, FL
and Lake Mary Psychiatric Services
Lake Mary, FL

Drs. Patel and Sallee respond

Dr. Mota-Castillo’s argument is most often stated from the opposite point of view that bipolar symptoms, particularly in patients age <10, are almost indistinguishable from those of ADHD. Our article did not—and cannot—address this controversy.

Because the evidence has been inconclusive, it is unclear if comorbid bipolar disorder and ADHD result from overlapping DSM-IV-TR diagnostic criteria, or whether two concurrent disorders exist. Suffice it to say that ADHD and bipolar disorder have many phenotypes and are both highly—but distinctly—heritable.

Overlapping symptoms may confound clinical diagnosis and result in “false positives” but may not account for most bipolar youths with comorbid ADHD. In one study,¹ 56% of subjects with both disorders maintained a bipolar disorder diagnosis when overlapping ADHD symptoms were subtracted.

Combination pharmacotherapy is needed because mood stabilizers do not treat attention and neurocognitive problems associated with ADHD. Therefore, a psychostimulant trial may help euthymic bipolar children and adolescents. In a recent placebo-controlled study by Scheffer et al,² ADHD symptoms—as measured with the Clinical Global Impression of Improvement scale and based upon Conners’ Teachers and Parent Ratings—significantly improved among divalproex sodium responders receiving mixed amphetamine salts.

Dr. Mota-Castillo, however, brings up two important questions:

• Are childhood symptoms that result in ADHD diagnosis a prodromal manifestation of bipolar disorder in some patients? Data from the first 1,000 STEP-BD participants suggest that ADHD may be part of the developmental phenotype of bipolar disorder comorbidity. Participants with mood symptom onset before age 13 had higher rates of comorbid ADHD than did those whose mood symptoms surfaced later on.³
• Do psychostimulants hasten mood disorder onset in a child diagnosed with ADHD who has a high familial risk of a mood disorder? How these agents influence the course of bipolar disorder is unclear. DelBello et al⁴ reported that psychostimulant exposure may be a stressor in youths at risk for bipolar disorder, may progressively worsen affective symptoms over time, and may lead to earlier mood symptom onset.

Both questions need further exploration as the implications for clinical practice may be tremendous.

Results from numerous independent studies consistently suggest that patients can be diagnosed with comorbid bipolar disorder and ADHD. More research is needed, however, to solve this diagnostic conundrum.

Nick C. Patel, PharmD, PhD
Assistant professor
Departments of pharmacy practice and psychiatry
Floyd R. Sallee, MD, PhD
Professor, department of psychiatry
University of Cincinnati

“What’s the best treatment for comorbid ADHD/bipolar mania?” by Drs. Nick C. Patel and Floyd R. Sallee (Current Psychiatry, April 2005) was well-written and offers excellent treatment guidelines. However, the idea that patients can have comorbid bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) is a fallacy.

I challenge any colleague, from the leading expert to the most recent graduate, to present a bona fide case of “comorbid” ADHD/bipolar disorder. I can prove that only one diagnosis is correct because:

• Bipolar disorder is more heritable than other psychiatric illnesses. Many patients labeled as having “comorbid” bipolar disorder and ADHD have parents with bipolar disorder or schizophrenia or are in foster care and their biological parents’ histories are unknown.
• I’ve seen hundreds of patients enter full-blown psychosis after another clinician put them on amphetamines or antidepressants while being treated for ADHD.
• Bipolar disorder can explain any so-called ADHD symptom.
• ADHD does not include moodiness or predatory aggression.

Over 10 years, I have diagnosed three or four patients as having comorbid bipolar disorder and ADHD. After a few years and inpatient treatments, these patients proved the second diagnosis wrong. We can decrease costs and avoid patients’ suffering by refining diagnostic criteria.

Manuel Mota-Castillo, MD, medical director
The Grove Academy, Sanford, FL
and Lake Mary Psychiatric Services
Lake Mary, FL

Drs. Patel and Sallee respond

Dr. Mota-Castillo’s argument is most often stated from the opposite point of view that bipolar symptoms, particularly in patients age <10, are almost indistinguishable from those of ADHD. Our article did not—and cannot—address this controversy.

Because the evidence has been inconclusive, it is unclear if comorbid bipolar disorder and ADHD result from overlapping DSM-IV-TR diagnostic criteria, or whether two concurrent disorders exist. Suffice it to say that ADHD and bipolar disorder have many phenotypes and are both highly—but distinctly—heritable.

Overlapping symptoms may confound clinical diagnosis and result in “false positives” but may not account for most bipolar youths with comorbid ADHD. In one study,¹ 56% of subjects with both disorders maintained a bipolar disorder diagnosis when overlapping ADHD symptoms were subtracted.

Combination pharmacotherapy is needed because mood stabilizers do not treat attention and neurocognitive problems associated with ADHD. Therefore, a psychostimulant trial may help euthymic bipolar children and adolescents. In a recent placebo-controlled study by Scheffer et al,² ADHD symptoms—as measured with the Clinical Global Impression of Improvement scale and based upon Conners’ Teachers and Parent Ratings—significantly improved among divalproex sodium responders receiving mixed amphetamine salts.

Dr. Mota-Castillo, however, brings up two important questions:

• Are childhood symptoms that result in ADHD diagnosis a prodromal manifestation of bipolar disorder in some patients? Data from the first 1,000 STEP-BD participants suggest that ADHD may be part of the developmental phenotype of bipolar disorder comorbidity. Participants with mood symptom onset before age 13 had higher rates of comorbid ADHD than did those whose mood symptoms surfaced later on.³
• Do psychostimulants hasten mood disorder onset in a child diagnosed with ADHD who has a high familial risk of a mood disorder? How these agents influence the course of bipolar disorder is unclear. DelBello et al⁴ reported that psychostimulant exposure may be a stressor in youths at risk for bipolar disorder, may progressively worsen affective symptoms over time, and may lead to earlier mood symptom onset.

Both questions need further exploration as the implications for clinical practice may be tremendous.

Results from numerous independent studies consistently suggest that patients can be diagnosed with comorbid bipolar disorder and ADHD. More research is needed, however, to solve this diagnostic conundrum.

Nick C. Patel, PharmD, PhD
Assistant professor
Departments of pharmacy practice and psychiatry
Floyd R. Sallee, MD, PhD
Professor, department of psychiatry
University of Cincinnati

BIRMINGHAM, ENGLAND — All patients with systemic lupus erythematosus who are taking 7.5 mg prednisone or more daily should be treated to prevent bone loss, Bevra Hahn, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Almost everyone loses bone mass at that level of steroid treatment, and relatively rapidly. “We know most bone loss occurs in the first 12 months of steroid treatment, so there isn't any point … waiting until the disease goes into remission—and lupus hardly ever goes into true remission—or waiting until they are better or their drug regimen is simpler,” she said.

Despite the fact that estrogen therapy is “out,” there are still treatment options. Calcium plus vitamin D supplementation is a typical initial approach, and has a small but measurable impact on reducing the degree of bone loss.

Another choice would be to use a vitamin D metabolite such as calcitriol. “These are more effective, but if you use a vitamin D metabolite, don't give supplemental calcium and be sure to monitor for hypercalcemia and maybe even hypercalcuria if you are practicing in an area where there are a lot of renal stones,” said Dr. Hahn, professor of medicine and chief of rheumatology, University of California, Los Angeles. Hypercalcemia is particularly hazardous when patients are acutely ill and take to bed. The drug should be stopped at that time, she said.

But there's no question in 2005 that bisphosphonate therapy is the most effective strategy to prevent bone loss in steroid-induced osteoporosis, she said. In fact, calcium plus ordinary vitamin D has been used as the placebo in a lot of the clinical trials of bisphosphonates.

“It doesn't matter which one you choose—whichever one you like. Now that Fosamax comes in a liquid I have a lot more patients who can tolerate bisphosphonate therapy,” she said. Liquid alendronate causes less esophageal irritation and gastric distress than the capsules, she said.

Another option for certain patients is treatment with the anabolic hormone PTH 1–34 (teriparatide, Forteo). This drug is useful for patients who have very low bone turnover and are continuing to fracture despite treatment with bisphosphonates, active vitamin D, and calcitonin, she said.

In some patients it isn't enough to turn the osteoclast off, which is how these drugs work. For these patients it's also necessary to turn the osteoblast on, which is what PTH does, she said.

PTH stimulates osteoblast accumulation and bone formation through receptor signals that modulate osteoblast proliferation and maturation. It also increases the lifespan and productivity of the osteoblast by preventing apoptosis (Treat. Endocrinol. 2002:1;175–90).

Unfortunately, patients don't like to take this drug because it's injectable and must be taken every day or every other day. But three other formulations, two injectable and one oral, are now in clinical trials (Expert Opin. Investig. Drugs 2005;14:251–64).

One caution is needed with using PTH in patients with lupus. “This is not recommended by anybody but me, but I think you should screen your patients for hyperparathyroidism before you start PTH. I have found elevated levels of parathyroid hormone in one-third of my lupus patients, and we shouldn't be giving PTH to people who already have primary hyperparathyroidism,” she said.

BIRMINGHAM, ENGLAND — All patients with systemic lupus erythematosus who are taking 7.5 mg prednisone or more daily should be treated to prevent bone loss, Bevra Hahn, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Almost everyone loses bone mass at that level of steroid treatment, and relatively rapidly. “We know most bone loss occurs in the first 12 months of steroid treatment, so there isn't any point … waiting until the disease goes into remission—and lupus hardly ever goes into true remission—or waiting until they are better or their drug regimen is simpler,” she said.

Despite the fact that estrogen therapy is “out,” there are still treatment options. Calcium plus vitamin D supplementation is a typical initial approach, and has a small but measurable impact on reducing the degree of bone loss.

Another choice would be to use a vitamin D metabolite such as calcitriol. “These are more effective, but if you use a vitamin D metabolite, don't give supplemental calcium and be sure to monitor for hypercalcemia and maybe even hypercalcuria if you are practicing in an area where there are a lot of renal stones,” said Dr. Hahn, professor of medicine and chief of rheumatology, University of California, Los Angeles. Hypercalcemia is particularly hazardous when patients are acutely ill and take to bed. The drug should be stopped at that time, she said.

But there's no question in 2005 that bisphosphonate therapy is the most effective strategy to prevent bone loss in steroid-induced osteoporosis, she said. In fact, calcium plus ordinary vitamin D has been used as the placebo in a lot of the clinical trials of bisphosphonates.

“It doesn't matter which one you choose—whichever one you like. Now that Fosamax comes in a liquid I have a lot more patients who can tolerate bisphosphonate therapy,” she said. Liquid alendronate causes less esophageal irritation and gastric distress than the capsules, she said.

Another option for certain patients is treatment with the anabolic hormone PTH 1–34 (teriparatide, Forteo). This drug is useful for patients who have very low bone turnover and are continuing to fracture despite treatment with bisphosphonates, active vitamin D, and calcitonin, she said.

In some patients it isn't enough to turn the osteoclast off, which is how these drugs work. For these patients it's also necessary to turn the osteoblast on, which is what PTH does, she said.

PTH stimulates osteoblast accumulation and bone formation through receptor signals that modulate osteoblast proliferation and maturation. It also increases the lifespan and productivity of the osteoblast by preventing apoptosis (Treat. Endocrinol. 2002:1;175–90).

Unfortunately, patients don't like to take this drug because it's injectable and must be taken every day or every other day. But three other formulations, two injectable and one oral, are now in clinical trials (Expert Opin. Investig. Drugs 2005;14:251–64).

One caution is needed with using PTH in patients with lupus. “This is not recommended by anybody but me, but I think you should screen your patients for hyperparathyroidism before you start PTH. I have found elevated levels of parathyroid hormone in one-third of my lupus patients, and we shouldn't be giving PTH to people who already have primary hyperparathyroidism,” she said.

BIRMINGHAM, ENGLAND — All patients with systemic lupus erythematosus who are taking 7.5 mg prednisone or more daily should be treated to prevent bone loss, Bevra Hahn, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Almost everyone loses bone mass at that level of steroid treatment, and relatively rapidly. “We know most bone loss occurs in the first 12 months of steroid treatment, so there isn't any point … waiting until the disease goes into remission—and lupus hardly ever goes into true remission—or waiting until they are better or their drug regimen is simpler,” she said.

Despite the fact that estrogen therapy is “out,” there are still treatment options. Calcium plus vitamin D supplementation is a typical initial approach, and has a small but measurable impact on reducing the degree of bone loss.

Another choice would be to use a vitamin D metabolite such as calcitriol. “These are more effective, but if you use a vitamin D metabolite, don't give supplemental calcium and be sure to monitor for hypercalcemia and maybe even hypercalcuria if you are practicing in an area where there are a lot of renal stones,” said Dr. Hahn, professor of medicine and chief of rheumatology, University of California, Los Angeles. Hypercalcemia is particularly hazardous when patients are acutely ill and take to bed. The drug should be stopped at that time, she said.

But there's no question in 2005 that bisphosphonate therapy is the most effective strategy to prevent bone loss in steroid-induced osteoporosis, she said. In fact, calcium plus ordinary vitamin D has been used as the placebo in a lot of the clinical trials of bisphosphonates.

“It doesn't matter which one you choose—whichever one you like. Now that Fosamax comes in a liquid I have a lot more patients who can tolerate bisphosphonate therapy,” she said. Liquid alendronate causes less esophageal irritation and gastric distress than the capsules, she said.

Another option for certain patients is treatment with the anabolic hormone PTH 1–34 (teriparatide, Forteo). This drug is useful for patients who have very low bone turnover and are continuing to fracture despite treatment with bisphosphonates, active vitamin D, and calcitonin, she said.

In some patients it isn't enough to turn the osteoclast off, which is how these drugs work. For these patients it's also necessary to turn the osteoblast on, which is what PTH does, she said.

PTH stimulates osteoblast accumulation and bone formation through receptor signals that modulate osteoblast proliferation and maturation. It also increases the lifespan and productivity of the osteoblast by preventing apoptosis (Treat. Endocrinol. 2002:1;175–90).

Unfortunately, patients don't like to take this drug because it's injectable and must be taken every day or every other day. But three other formulations, two injectable and one oral, are now in clinical trials (Expert Opin. Investig. Drugs 2005;14:251–64).

One caution is needed with using PTH in patients with lupus. “This is not recommended by anybody but me, but I think you should screen your patients for hyperparathyroidism before you start PTH. I have found elevated levels of parathyroid hormone in one-third of my lupus patients, and we shouldn't be giving PTH to people who already have primary hyperparathyroidism,” she said.

VIENNA — B-cell depletion with rituximab led to significant improvements in patients with CNS neuropsychiatric disability associated with systemic lupus erythematosus, according to a preliminary report presented by C. Michael Neuwelt, M.D., at the annual European congress of rheumatology.

In his investigation, Dr. Neuwelt, of the University of California, San Francisco, and Stanford University, Palo Alto, studied 22 patients who met American College of Rheumatology criteria for CNS-NPSLE disability.

In addition, at baseline, patients met at least one of three criteria: abnormal brain MRI, severe progression of cognitive impairment as shown by neuropsychological testing, or cerebrospinal fluid pleocytosis and/or intrathecal elevation of IgG synthesis and/or oligoclonal banding.

Among the participants in the single-center study, 12 were treated with rituximab monotherapy, 7 were treated with a combination of rituximab and IV cyclophosphamide (IV-CYC), and 3 patients received plasmapheresis synchronized with IV-CYC and were maintained on rituximab for prolonged B-cell suppression.

After up to 18 months' follow up, 72% of the 19 patients treated with either rituximab alone or in combination with IV-CYC showed improvement. The three patients on triple therapy did not improve and required new therapy regimens.

In addition to monitoring changes in the objective parameters, patient outcomes were measured using several standard SLE disease activity indices.

Dr. Neuwelt emphasized that in at least one case, the patient actually had a disease flare with worsening brain lesions following a switch from her prestudy regimen of IV-CYC to rituximab monotherapy. In her case, combination IV-CYC and rituximab led to significant improvements over baseline (see MRI images before and after combination therapy).

Further research is needed to identify the best candidates for rituximab monotherapy and which patients will require combination therapy, said Dr. Neuwelt, who is on the advisory board for Genentech Inc., the manufacturer of rituximab (Rituxan). However, he did not receive funding for his study.

Outcomes from his observational study of 22 patients compared well to earlier, published reports of similar patients treated with IV-CYC with and without plasmapheresis, Dr. Neuwelt explained at the meeting, sponsored by the European League Against Rheumatism.

Those previous reports, which defined outcome end points in the same manner as the current study, found a 61% rate of improvement among 31 severe CNS-NPSLE patients treated with IV-CYC (Am. J. Med. 1995;98:32–41). Another study, also conducted by Dr. Neuwelt, found a 74% rate of improvement among 26 severe CNS-NPSLE patients treated with plasmapheresis either alone or synchronized with cyclophosphamide (Ther. Apher. Dial. 2003;7:173–82).

The lack of head-to-head trials comparing rituximab to other therapies is indicative of the challenges facing lupus-therapy investigations. Clinical trials of lupus patients are notoriously difficult to conduct, given the heterogeneity of the patient population. And CNS effects are the most difficult aspect of lupus to pin down, Dr. Neuwelt said in an interview.

“We don't know a lot about the pathogenic mechanisms” that lead to neuropsychiatric manifestations of SLE. “That's an area that we know the least about,” and yet it takes a considerable toll on quality of life, he said. There are no exact end points to measure changes in this manifestation, which makes it a difficult aspect of SLE to study.

He added that better tools to measure patient-centered outcomes in SLE—specifically, ones targeting neuropsychiatric markers—need to be developed.

The justification for trying rituximab in a CNS-NPSLE population is speculative at this time. However, similarities between lupus of the brain and multiple sclerosis exist. In MS, B cells and antibody-mediated demyelination comes from histopathologic studies of CNS tissue and analysis of CSF. Similar studies need to be done in the CNS tissue and CSF of CNS-NPSLE patients, Dr. Neuwelt said.

The prevalence of neuropsychiatric disorders in SLE has been found to range from 37% to 95% in various studies. The most common effects are cognitive dysfunction (55%–80%), headache (24%–72%), mood disorder (14%–57%), cerebrovascular disease (5%–18%), seizures (6%–51%), polyneuropathy (3%–28%), anxiety (7%–24%), and psychosis (0%–8%), according to John Hanly, M.D., head of the rheumatology division at Dalhousie University, Halifax, Nova Scotia. Dr. Hanly also presented on CNS-NPSLE at the meeting.

A 45-year-old woman was switched from IV CYC to rituximab monotherapy. Shortly after the switch, the patient's disease flared and a brain MRI in April (left) showed progression of her lesions. IV CYC was then added back to her regimen. A follow-up MRI in July showed the number of lesions was reduced on the combination. Photos courtesy Dr. C. Michael Neuwelt

VIENNA — B-cell depletion with rituximab led to significant improvements in patients with CNS neuropsychiatric disability associated with systemic lupus erythematosus, according to a preliminary report presented by C. Michael Neuwelt, M.D., at the annual European congress of rheumatology.

In his investigation, Dr. Neuwelt, of the University of California, San Francisco, and Stanford University, Palo Alto, studied 22 patients who met American College of Rheumatology criteria for CNS-NPSLE disability.

In addition, at baseline, patients met at least one of three criteria: abnormal brain MRI, severe progression of cognitive impairment as shown by neuropsychological testing, or cerebrospinal fluid pleocytosis and/or intrathecal elevation of IgG synthesis and/or oligoclonal banding.

Among the participants in the single-center study, 12 were treated with rituximab monotherapy, 7 were treated with a combination of rituximab and IV cyclophosphamide (IV-CYC), and 3 patients received plasmapheresis synchronized with IV-CYC and were maintained on rituximab for prolonged B-cell suppression.

After up to 18 months' follow up, 72% of the 19 patients treated with either rituximab alone or in combination with IV-CYC showed improvement. The three patients on triple therapy did not improve and required new therapy regimens.

In addition to monitoring changes in the objective parameters, patient outcomes were measured using several standard SLE disease activity indices.

Dr. Neuwelt emphasized that in at least one case, the patient actually had a disease flare with worsening brain lesions following a switch from her prestudy regimen of IV-CYC to rituximab monotherapy. In her case, combination IV-CYC and rituximab led to significant improvements over baseline (see MRI images before and after combination therapy).

Further research is needed to identify the best candidates for rituximab monotherapy and which patients will require combination therapy, said Dr. Neuwelt, who is on the advisory board for Genentech Inc., the manufacturer of rituximab (Rituxan). However, he did not receive funding for his study.

Outcomes from his observational study of 22 patients compared well to earlier, published reports of similar patients treated with IV-CYC with and without plasmapheresis, Dr. Neuwelt explained at the meeting, sponsored by the European League Against Rheumatism.

Those previous reports, which defined outcome end points in the same manner as the current study, found a 61% rate of improvement among 31 severe CNS-NPSLE patients treated with IV-CYC (Am. J. Med. 1995;98:32–41). Another study, also conducted by Dr. Neuwelt, found a 74% rate of improvement among 26 severe CNS-NPSLE patients treated with plasmapheresis either alone or synchronized with cyclophosphamide (Ther. Apher. Dial. 2003;7:173–82).

The lack of head-to-head trials comparing rituximab to other therapies is indicative of the challenges facing lupus-therapy investigations. Clinical trials of lupus patients are notoriously difficult to conduct, given the heterogeneity of the patient population. And CNS effects are the most difficult aspect of lupus to pin down, Dr. Neuwelt said in an interview.

“We don't know a lot about the pathogenic mechanisms” that lead to neuropsychiatric manifestations of SLE. “That's an area that we know the least about,” and yet it takes a considerable toll on quality of life, he said. There are no exact end points to measure changes in this manifestation, which makes it a difficult aspect of SLE to study.

He added that better tools to measure patient-centered outcomes in SLE—specifically, ones targeting neuropsychiatric markers—need to be developed.

The justification for trying rituximab in a CNS-NPSLE population is speculative at this time. However, similarities between lupus of the brain and multiple sclerosis exist. In MS, B cells and antibody-mediated demyelination comes from histopathologic studies of CNS tissue and analysis of CSF. Similar studies need to be done in the CNS tissue and CSF of CNS-NPSLE patients, Dr. Neuwelt said.

The prevalence of neuropsychiatric disorders in SLE has been found to range from 37% to 95% in various studies. The most common effects are cognitive dysfunction (55%–80%), headache (24%–72%), mood disorder (14%–57%), cerebrovascular disease (5%–18%), seizures (6%–51%), polyneuropathy (3%–28%), anxiety (7%–24%), and psychosis (0%–8%), according to John Hanly, M.D., head of the rheumatology division at Dalhousie University, Halifax, Nova Scotia. Dr. Hanly also presented on CNS-NPSLE at the meeting.

A 45-year-old woman was switched from IV CYC to rituximab monotherapy. Shortly after the switch, the patient's disease flared and a brain MRI in April (left) showed progression of her lesions. IV CYC was then added back to her regimen. A follow-up MRI in July showed the number of lesions was reduced on the combination. Photos courtesy Dr. C. Michael Neuwelt

VIENNA — B-cell depletion with rituximab led to significant improvements in patients with CNS neuropsychiatric disability associated with systemic lupus erythematosus, according to a preliminary report presented by C. Michael Neuwelt, M.D., at the annual European congress of rheumatology.

In his investigation, Dr. Neuwelt, of the University of California, San Francisco, and Stanford University, Palo Alto, studied 22 patients who met American College of Rheumatology criteria for CNS-NPSLE disability.

In addition, at baseline, patients met at least one of three criteria: abnormal brain MRI, severe progression of cognitive impairment as shown by neuropsychological testing, or cerebrospinal fluid pleocytosis and/or intrathecal elevation of IgG synthesis and/or oligoclonal banding.

Among the participants in the single-center study, 12 were treated with rituximab monotherapy, 7 were treated with a combination of rituximab and IV cyclophosphamide (IV-CYC), and 3 patients received plasmapheresis synchronized with IV-CYC and were maintained on rituximab for prolonged B-cell suppression.

After up to 18 months' follow up, 72% of the 19 patients treated with either rituximab alone or in combination with IV-CYC showed improvement. The three patients on triple therapy did not improve and required new therapy regimens.

In addition to monitoring changes in the objective parameters, patient outcomes were measured using several standard SLE disease activity indices.

Dr. Neuwelt emphasized that in at least one case, the patient actually had a disease flare with worsening brain lesions following a switch from her prestudy regimen of IV-CYC to rituximab monotherapy. In her case, combination IV-CYC and rituximab led to significant improvements over baseline (see MRI images before and after combination therapy).

Further research is needed to identify the best candidates for rituximab monotherapy and which patients will require combination therapy, said Dr. Neuwelt, who is on the advisory board for Genentech Inc., the manufacturer of rituximab (Rituxan). However, he did not receive funding for his study.

Outcomes from his observational study of 22 patients compared well to earlier, published reports of similar patients treated with IV-CYC with and without plasmapheresis, Dr. Neuwelt explained at the meeting, sponsored by the European League Against Rheumatism.

Those previous reports, which defined outcome end points in the same manner as the current study, found a 61% rate of improvement among 31 severe CNS-NPSLE patients treated with IV-CYC (Am. J. Med. 1995;98:32–41). Another study, also conducted by Dr. Neuwelt, found a 74% rate of improvement among 26 severe CNS-NPSLE patients treated with plasmapheresis either alone or synchronized with cyclophosphamide (Ther. Apher. Dial. 2003;7:173–82).

The lack of head-to-head trials comparing rituximab to other therapies is indicative of the challenges facing lupus-therapy investigations. Clinical trials of lupus patients are notoriously difficult to conduct, given the heterogeneity of the patient population. And CNS effects are the most difficult aspect of lupus to pin down, Dr. Neuwelt said in an interview.

“We don't know a lot about the pathogenic mechanisms” that lead to neuropsychiatric manifestations of SLE. “That's an area that we know the least about,” and yet it takes a considerable toll on quality of life, he said. There are no exact end points to measure changes in this manifestation, which makes it a difficult aspect of SLE to study.

He added that better tools to measure patient-centered outcomes in SLE—specifically, ones targeting neuropsychiatric markers—need to be developed.

The justification for trying rituximab in a CNS-NPSLE population is speculative at this time. However, similarities between lupus of the brain and multiple sclerosis exist. In MS, B cells and antibody-mediated demyelination comes from histopathologic studies of CNS tissue and analysis of CSF. Similar studies need to be done in the CNS tissue and CSF of CNS-NPSLE patients, Dr. Neuwelt said.

The prevalence of neuropsychiatric disorders in SLE has been found to range from 37% to 95% in various studies. The most common effects are cognitive dysfunction (55%–80%), headache (24%–72%), mood disorder (14%–57%), cerebrovascular disease (5%–18%), seizures (6%–51%), polyneuropathy (3%–28%), anxiety (7%–24%), and psychosis (0%–8%), according to John Hanly, M.D., head of the rheumatology division at Dalhousie University, Halifax, Nova Scotia. Dr. Hanly also presented on CNS-NPSLE at the meeting.

A 45-year-old woman was switched from IV CYC to rituximab monotherapy. Shortly after the switch, the patient's disease flared and a brain MRI in April (left) showed progression of her lesions. IV CYC was then added back to her regimen. A follow-up MRI in July showed the number of lesions was reduced on the combination. Photos courtesy Dr. C. Michael Neuwelt

BOSTON — Patients with spondyloarthropathy (SpA) who undergo therapy with the tumor necrosis factor-α inhibitor etanercept are at low risk of developing antibodies associated with systemic lupus erythematosus, according to a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

Although these potentially harmful antibodies seem to be increased in patients receiving infliximab, neither of the biologics induced lupus-like symptoms, one of the feared side effects of anti-TNF-α therapy.

Recent studies have shown promising results of anti-TNF-α therapy in patients with SpA. Many more have documented their efficacy in rheumatoid arthritis (RA). But enthusiasm for the new drugs has been muted by widespread concern over side effects that range from headache to infection and lymphoma.

In addition, numerous reports in the RA literature now show that infliximab induces antibodies associated with SLE. But the actual induction of clinically relevant lupus appears to be rare, and tracing its origin to drug-induced TNF-α blockade has been difficult to do.

In a previous study, Leen De Rycke, M.D., and colleagues from Ghent University Hospital, Belgium, reported for the first time that RA and SpA patients taking infliximab tended to produce high levels of the SLE antibodies, antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies (Arthritis Rheum. 2003;48:1015–23).

In their new study, they set out to see what happened to these patients over the long term, and whether etanercept therapy induces high antibody responses similar to those of infliximab.

Dr. De Rycke and associates followed 20 SpA patients for 1 year of treatment with etanercept. They compared the number of patients who developed newly induced autoantibodies in this cohort with those of 34 SpA patients who underwent infliximab therapy for 2 years.

On average, patients in the etanercept group were a decade younger (37 years of age) than those in the infliximab group (47 years). Autoimmunity at baseline was low. None of the patients was taking concomitant methotrexate. After 1 year, 10% of the SpA patients on etanercept had evidence of newly induced ANAs compared with 62% of the patients taking infliximab.

Similarly, newly induced anti-dsDNA antibodies were present in the sera of 10% of patients receiving etanercept, and in 71% of those receiving infliximab. Neither drug induced anti-ENA or antihistone antibodies.

Nor did any patients in either group develop lupus-like symptoms. Titers of IgM, but not IgG, anticardiolipin were selectively increased after infliximab but not etanercept therapy. The anti-dsDNA antibodies were predominantly of the immunoglobulin M (IgM) and immunoglobulin G (IgG) isotype. Lupus-associated anti-dsDNA antibodies are classically of the IgG isotope.

“This study indicates that the prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF-α blockers,” Dr. De Rycke and colleagues concluded. Moreover, it “is not associated with clinically relevant lupus symptoms,” they said.

BOSTON — Patients with spondyloarthropathy (SpA) who undergo therapy with the tumor necrosis factor-α inhibitor etanercept are at low risk of developing antibodies associated with systemic lupus erythematosus, according to a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

Although these potentially harmful antibodies seem to be increased in patients receiving infliximab, neither of the biologics induced lupus-like symptoms, one of the feared side effects of anti-TNF-α therapy.

Recent studies have shown promising results of anti-TNF-α therapy in patients with SpA. Many more have documented their efficacy in rheumatoid arthritis (RA). But enthusiasm for the new drugs has been muted by widespread concern over side effects that range from headache to infection and lymphoma.

In addition, numerous reports in the RA literature now show that infliximab induces antibodies associated with SLE. But the actual induction of clinically relevant lupus appears to be rare, and tracing its origin to drug-induced TNF-α blockade has been difficult to do.

In a previous study, Leen De Rycke, M.D., and colleagues from Ghent University Hospital, Belgium, reported for the first time that RA and SpA patients taking infliximab tended to produce high levels of the SLE antibodies, antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies (Arthritis Rheum. 2003;48:1015–23).

In their new study, they set out to see what happened to these patients over the long term, and whether etanercept therapy induces high antibody responses similar to those of infliximab.

Dr. De Rycke and associates followed 20 SpA patients for 1 year of treatment with etanercept. They compared the number of patients who developed newly induced autoantibodies in this cohort with those of 34 SpA patients who underwent infliximab therapy for 2 years.

On average, patients in the etanercept group were a decade younger (37 years of age) than those in the infliximab group (47 years). Autoimmunity at baseline was low. None of the patients was taking concomitant methotrexate. After 1 year, 10% of the SpA patients on etanercept had evidence of newly induced ANAs compared with 62% of the patients taking infliximab.

Similarly, newly induced anti-dsDNA antibodies were present in the sera of 10% of patients receiving etanercept, and in 71% of those receiving infliximab. Neither drug induced anti-ENA or antihistone antibodies.

Nor did any patients in either group develop lupus-like symptoms. Titers of IgM, but not IgG, anticardiolipin were selectively increased after infliximab but not etanercept therapy. The anti-dsDNA antibodies were predominantly of the immunoglobulin M (IgM) and immunoglobulin G (IgG) isotype. Lupus-associated anti-dsDNA antibodies are classically of the IgG isotope.

“This study indicates that the prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF-α blockers,” Dr. De Rycke and colleagues concluded. Moreover, it “is not associated with clinically relevant lupus symptoms,” they said.

BOSTON — Patients with spondyloarthropathy (SpA) who undergo therapy with the tumor necrosis factor-α inhibitor etanercept are at low risk of developing antibodies associated with systemic lupus erythematosus, according to a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

Although these potentially harmful antibodies seem to be increased in patients receiving infliximab, neither of the biologics induced lupus-like symptoms, one of the feared side effects of anti-TNF-α therapy.

Recent studies have shown promising results of anti-TNF-α therapy in patients with SpA. Many more have documented their efficacy in rheumatoid arthritis (RA). But enthusiasm for the new drugs has been muted by widespread concern over side effects that range from headache to infection and lymphoma.

In addition, numerous reports in the RA literature now show that infliximab induces antibodies associated with SLE. But the actual induction of clinically relevant lupus appears to be rare, and tracing its origin to drug-induced TNF-α blockade has been difficult to do.

In a previous study, Leen De Rycke, M.D., and colleagues from Ghent University Hospital, Belgium, reported for the first time that RA and SpA patients taking infliximab tended to produce high levels of the SLE antibodies, antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies (Arthritis Rheum. 2003;48:1015–23).

In their new study, they set out to see what happened to these patients over the long term, and whether etanercept therapy induces high antibody responses similar to those of infliximab.

Dr. De Rycke and associates followed 20 SpA patients for 1 year of treatment with etanercept. They compared the number of patients who developed newly induced autoantibodies in this cohort with those of 34 SpA patients who underwent infliximab therapy for 2 years.

On average, patients in the etanercept group were a decade younger (37 years of age) than those in the infliximab group (47 years). Autoimmunity at baseline was low. None of the patients was taking concomitant methotrexate. After 1 year, 10% of the SpA patients on etanercept had evidence of newly induced ANAs compared with 62% of the patients taking infliximab.

Similarly, newly induced anti-dsDNA antibodies were present in the sera of 10% of patients receiving etanercept, and in 71% of those receiving infliximab. Neither drug induced anti-ENA or antihistone antibodies.

Nor did any patients in either group develop lupus-like symptoms. Titers of IgM, but not IgG, anticardiolipin were selectively increased after infliximab but not etanercept therapy. The anti-dsDNA antibodies were predominantly of the immunoglobulin M (IgM) and immunoglobulin G (IgG) isotype. Lupus-associated anti-dsDNA antibodies are classically of the IgG isotope.

“This study indicates that the prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF-α blockers,” Dr. De Rycke and colleagues concluded. Moreover, it “is not associated with clinically relevant lupus symptoms,” they said.

NEW YORK — Treatment of Wegener's granulomatosis continues to challenge and evolve, as researchers investigate the complex molecular cross-talk underlying immune dysfunction, looking for new ways to target therapy, and clinicians seek new ways to balance necessarily aggressive cytotoxic treatment against the potential for serious adverse events.

Standard induction treatment for severe vasculitis associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) remains cyclophosphamide plus glucocorticoids—a regimen that is lifesaving, Gary S. Hoffman, M.D., said at a rheumatology meeting sponsored by New York University.

But because of the high incidence of bladder cancer and other serious toxicities associated with long-term use of cyclophosphamide, once remission is achieved, maintenance therapy with methotrexate or azathioprine is now preferred, he said.

Relapse remains problematic, however, and a subset of patients do not respond to the most cytotoxic cyclophosphamide-based regimen.

For these patients, a potential new approach has emerged: B-cell depletion with rituximab, said Dr. Hoffman, chair of the department of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

A group of 11 patients who had active, ANCA-positive vasculitis and either did not respond to cyclophosphamide or who had contraindications to its use were given infusions of rituximab (Rituxan) plus glucocorticoids on a compassionate use basis. Ten of the patients had Wegener's granulomatosis, and one had a related ANCA-associated vasculitis, microscopic polyangiitis.

Not only did all 11 achieve remission, but they also were able to discontinue steroids, which has not been possible before, said Dr. Hoffman, who was not involved in the study.

All patients had significant decreases in ANCA, which are thought to mediate the glomerulonephritis and small vessel vasculitis, and 8 of the 11 became ANCA negative.

B-cell depletion typically persists for months following rituximab treatment; all patients remained in remission while B cells were undetectable.

Reappearance of B cells occurred in nine patients, 4–12 months after infusion. Two patients experienced disease relapse following discontinuation of glucocorticoids but recovered after resuming the rituximab/glucocorticoid regimen. Three others whose ANCA titers began to rise were retreated preemptively with rituximab alone and have remained in remission (Arthritis Rheum. 2005;52:262–8). The remaining four patients whose B cells repopulated did not revert to ANCA positivity.

Rituximab targets the CD20 receptor on the surface of B cells, and one rationale for using the drug in Wegener's granulomatosis is that it is able to deplete CD20-expressing precursors of ANCA-producing plasma cells (Arthritis Rheum. 2005;52:1–5).

A randomized, double-blind trial, Rituximab in ANCA-Associated Vasculitis (RAVE) is underway, with the goal of addressing the issue of whether targeted therapy, rather than broad-based immunosuppression, can provide enduring remission.

Many mediators other than B cells are involved in the inflammatory process of vasculitis, including dendritic cells, macrophages, and various different cytokines that interact with one another.

A previous trial evaluated the tumor necrosis factor (TNF)-α blocking agent etanercept (Enbrel), because the evidence suggested that this cytokine plays a role.

But a randomized, placebo-controlled trial that included 174 patients from eight centers found no benefit in the addition of etanercept to standard therapy. Furthermore, six patients who were taking etanercept plus cyclophosphamide developed solid tumors (N. Engl. J. Med. 2005;352:351–61).

“We didn't see this with people who were on methotrexate plus etanercept, and it's a major concern,” said Dr. Hoffman, who was coprincipal investigator for the trial.

“The new opportunities for selective targets certainly are seductive, and we hope they will work, but we cannot dismiss what we've learned from the history of this disease, which is that it carries a very high risk of morbidity and mortality, and that although our conventional therapy has risks, it is lifesaving,” he said.

Before glucocorticoids began being used for Wegener's granulomatosis, survival was only 50% at 5 months, and most patients died within 2 years of diagnosis. Even with glucocorticoids, survival increased only slightly, to 50% at 1 year.

The addition of cyclophosphamide to the regimen, first reported by the National Institutes of Health in the early 1970s, increased survival to 80% at 8 years.

“But I think we still have a long road ahead of us. I hope the future looks great, but I view it with guarded optimism,” Dr. Hoffman said.

NEW YORK — Treatment of Wegener's granulomatosis continues to challenge and evolve, as researchers investigate the complex molecular cross-talk underlying immune dysfunction, looking for new ways to target therapy, and clinicians seek new ways to balance necessarily aggressive cytotoxic treatment against the potential for serious adverse events.

Standard induction treatment for severe vasculitis associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) remains cyclophosphamide plus glucocorticoids—a regimen that is lifesaving, Gary S. Hoffman, M.D., said at a rheumatology meeting sponsored by New York University.

But because of the high incidence of bladder cancer and other serious toxicities associated with long-term use of cyclophosphamide, once remission is achieved, maintenance therapy with methotrexate or azathioprine is now preferred, he said.

Relapse remains problematic, however, and a subset of patients do not respond to the most cytotoxic cyclophosphamide-based regimen.

For these patients, a potential new approach has emerged: B-cell depletion with rituximab, said Dr. Hoffman, chair of the department of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

A group of 11 patients who had active, ANCA-positive vasculitis and either did not respond to cyclophosphamide or who had contraindications to its use were given infusions of rituximab (Rituxan) plus glucocorticoids on a compassionate use basis. Ten of the patients had Wegener's granulomatosis, and one had a related ANCA-associated vasculitis, microscopic polyangiitis.

Not only did all 11 achieve remission, but they also were able to discontinue steroids, which has not been possible before, said Dr. Hoffman, who was not involved in the study.

All patients had significant decreases in ANCA, which are thought to mediate the glomerulonephritis and small vessel vasculitis, and 8 of the 11 became ANCA negative.

B-cell depletion typically persists for months following rituximab treatment; all patients remained in remission while B cells were undetectable.

Reappearance of B cells occurred in nine patients, 4–12 months after infusion. Two patients experienced disease relapse following discontinuation of glucocorticoids but recovered after resuming the rituximab/glucocorticoid regimen. Three others whose ANCA titers began to rise were retreated preemptively with rituximab alone and have remained in remission (Arthritis Rheum. 2005;52:262–8). The remaining four patients whose B cells repopulated did not revert to ANCA positivity.

Rituximab targets the CD20 receptor on the surface of B cells, and one rationale for using the drug in Wegener's granulomatosis is that it is able to deplete CD20-expressing precursors of ANCA-producing plasma cells (Arthritis Rheum. 2005;52:1–5).

A randomized, double-blind trial, Rituximab in ANCA-Associated Vasculitis (RAVE) is underway, with the goal of addressing the issue of whether targeted therapy, rather than broad-based immunosuppression, can provide enduring remission.

Many mediators other than B cells are involved in the inflammatory process of vasculitis, including dendritic cells, macrophages, and various different cytokines that interact with one another.

A previous trial evaluated the tumor necrosis factor (TNF)-α blocking agent etanercept (Enbrel), because the evidence suggested that this cytokine plays a role.

But a randomized, placebo-controlled trial that included 174 patients from eight centers found no benefit in the addition of etanercept to standard therapy. Furthermore, six patients who were taking etanercept plus cyclophosphamide developed solid tumors (N. Engl. J. Med. 2005;352:351–61).

“We didn't see this with people who were on methotrexate plus etanercept, and it's a major concern,” said Dr. Hoffman, who was coprincipal investigator for the trial.

“The new opportunities for selective targets certainly are seductive, and we hope they will work, but we cannot dismiss what we've learned from the history of this disease, which is that it carries a very high risk of morbidity and mortality, and that although our conventional therapy has risks, it is lifesaving,” he said.

Before glucocorticoids began being used for Wegener's granulomatosis, survival was only 50% at 5 months, and most patients died within 2 years of diagnosis. Even with glucocorticoids, survival increased only slightly, to 50% at 1 year.

The addition of cyclophosphamide to the regimen, first reported by the National Institutes of Health in the early 1970s, increased survival to 80% at 8 years.

“But I think we still have a long road ahead of us. I hope the future looks great, but I view it with guarded optimism,” Dr. Hoffman said.

NEW YORK — Treatment of Wegener's granulomatosis continues to challenge and evolve, as researchers investigate the complex molecular cross-talk underlying immune dysfunction, looking for new ways to target therapy, and clinicians seek new ways to balance necessarily aggressive cytotoxic treatment against the potential for serious adverse events.

Standard induction treatment for severe vasculitis associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) remains cyclophosphamide plus glucocorticoids—a regimen that is lifesaving, Gary S. Hoffman, M.D., said at a rheumatology meeting sponsored by New York University.

But because of the high incidence of bladder cancer and other serious toxicities associated with long-term use of cyclophosphamide, once remission is achieved, maintenance therapy with methotrexate or azathioprine is now preferred, he said.

Relapse remains problematic, however, and a subset of patients do not respond to the most cytotoxic cyclophosphamide-based regimen.

For these patients, a potential new approach has emerged: B-cell depletion with rituximab, said Dr. Hoffman, chair of the department of rheumatic and immunologic diseases at the Cleveland Clinic Foundation.

A group of 11 patients who had active, ANCA-positive vasculitis and either did not respond to cyclophosphamide or who had contraindications to its use were given infusions of rituximab (Rituxan) plus glucocorticoids on a compassionate use basis. Ten of the patients had Wegener's granulomatosis, and one had a related ANCA-associated vasculitis, microscopic polyangiitis.

Not only did all 11 achieve remission, but they also were able to discontinue steroids, which has not been possible before, said Dr. Hoffman, who was not involved in the study.

All patients had significant decreases in ANCA, which are thought to mediate the glomerulonephritis and small vessel vasculitis, and 8 of the 11 became ANCA negative.

B-cell depletion typically persists for months following rituximab treatment; all patients remained in remission while B cells were undetectable.

Reappearance of B cells occurred in nine patients, 4–12 months after infusion. Two patients experienced disease relapse following discontinuation of glucocorticoids but recovered after resuming the rituximab/glucocorticoid regimen. Three others whose ANCA titers began to rise were retreated preemptively with rituximab alone and have remained in remission (Arthritis Rheum. 2005;52:262–8). The remaining four patients whose B cells repopulated did not revert to ANCA positivity.

Rituximab targets the CD20 receptor on the surface of B cells, and one rationale for using the drug in Wegener's granulomatosis is that it is able to deplete CD20-expressing precursors of ANCA-producing plasma cells (Arthritis Rheum. 2005;52:1–5).

A randomized, double-blind trial, Rituximab in ANCA-Associated Vasculitis (RAVE) is underway, with the goal of addressing the issue of whether targeted therapy, rather than broad-based immunosuppression, can provide enduring remission.

Many mediators other than B cells are involved in the inflammatory process of vasculitis, including dendritic cells, macrophages, and various different cytokines that interact with one another.

A previous trial evaluated the tumor necrosis factor (TNF)-α blocking agent etanercept (Enbrel), because the evidence suggested that this cytokine plays a role.

But a randomized, placebo-controlled trial that included 174 patients from eight centers found no benefit in the addition of etanercept to standard therapy. Furthermore, six patients who were taking etanercept plus cyclophosphamide developed solid tumors (N. Engl. J. Med. 2005;352:351–61).

“We didn't see this with people who were on methotrexate plus etanercept, and it's a major concern,” said Dr. Hoffman, who was coprincipal investigator for the trial.

“The new opportunities for selective targets certainly are seductive, and we hope they will work, but we cannot dismiss what we've learned from the history of this disease, which is that it carries a very high risk of morbidity and mortality, and that although our conventional therapy has risks, it is lifesaving,” he said.

Before glucocorticoids began being used for Wegener's granulomatosis, survival was only 50% at 5 months, and most patients died within 2 years of diagnosis. Even with glucocorticoids, survival increased only slightly, to 50% at 1 year.

The addition of cyclophosphamide to the regimen, first reported by the National Institutes of Health in the early 1970s, increased survival to 80% at 8 years.

“But I think we still have a long road ahead of us. I hope the future looks great, but I view it with guarded optimism,” Dr. Hoffman said.

PONTE VEDRA BEACH, FLA. — When a coronary artery is too tight to accommodate a stent, it may be necessary to apply a little grease.

A lubricant suited to the job was an olive oil and egg yolk phospholipid-based emulsion sold commercially as Rotaglide, Mark Awar, M.D., and associates reported in a poster at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

The 20 patients in the series they reported on were those who failed initial stent placement out of 813 consecutive patients who underwent a percutaneous coronary intervention at Jefferson Medical College in Philadelphia.

In these 20 cases stent delivery was unsuccessful despite predilation and several other steps: substitution of a moderate-to-stiff guidewire, reattempts with a new guiding catheter or a new stent, use of a buddy wire, and in one case use of rotational atherectomy. After failed delivery, the stents were removed from their guiding catheters, saturated with Rotaglide using a 20-cc syringe, and a second delivery was immediately attempted.

Application of Rotaglide led to successful delivery for 17 of the 20 stents, reported Dr. Awar, a cardiologist at Jefferson. Angiography showed excellent anatomic results in all 17 patients. There were no major adverse coronary events or subacute stent thromboses.

All 20 patients had arteries with complex anatomy and unfavorable morphologic features: 17 (85%) had tortuous vessels, 13 (65%) had calcification, and 10 (50%) had diffuse disease (several patients had more than one feature). The target vessels included 10 left circumflex arteries, 8 right coronary arteries, and 2 left anterior descending arteries. Average patient age was 69 years, and 75% were men.

Use of Rotaglide to smooth the way for a stubborn stent had previously been reported in isolated case studies, but not in such a large series. Prior reports also have documented up to a 4% rate of failure in delivering stents to their target lesions (in this series the rate was 2.5%: 20 out of 813).

Rotaglide is sold by Boston Scientific to reduce catheter friction during rotational atherectomy.

The study was not sponsored by Boston Scientific.

PONTE VEDRA BEACH, FLA. — When a coronary artery is too tight to accommodate a stent, it may be necessary to apply a little grease.

A lubricant suited to the job was an olive oil and egg yolk phospholipid-based emulsion sold commercially as Rotaglide, Mark Awar, M.D., and associates reported in a poster at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

The 20 patients in the series they reported on were those who failed initial stent placement out of 813 consecutive patients who underwent a percutaneous coronary intervention at Jefferson Medical College in Philadelphia.

In these 20 cases stent delivery was unsuccessful despite predilation and several other steps: substitution of a moderate-to-stiff guidewire, reattempts with a new guiding catheter or a new stent, use of a buddy wire, and in one case use of rotational atherectomy. After failed delivery, the stents were removed from their guiding catheters, saturated with Rotaglide using a 20-cc syringe, and a second delivery was immediately attempted.

Application of Rotaglide led to successful delivery for 17 of the 20 stents, reported Dr. Awar, a cardiologist at Jefferson. Angiography showed excellent anatomic results in all 17 patients. There were no major adverse coronary events or subacute stent thromboses.

All 20 patients had arteries with complex anatomy and unfavorable morphologic features: 17 (85%) had tortuous vessels, 13 (65%) had calcification, and 10 (50%) had diffuse disease (several patients had more than one feature). The target vessels included 10 left circumflex arteries, 8 right coronary arteries, and 2 left anterior descending arteries. Average patient age was 69 years, and 75% were men.

Use of Rotaglide to smooth the way for a stubborn stent had previously been reported in isolated case studies, but not in such a large series. Prior reports also have documented up to a 4% rate of failure in delivering stents to their target lesions (in this series the rate was 2.5%: 20 out of 813).

Rotaglide is sold by Boston Scientific to reduce catheter friction during rotational atherectomy.

The study was not sponsored by Boston Scientific.

PONTE VEDRA BEACH, FLA. — When a coronary artery is too tight to accommodate a stent, it may be necessary to apply a little grease.

A lubricant suited to the job was an olive oil and egg yolk phospholipid-based emulsion sold commercially as Rotaglide, Mark Awar, M.D., and associates reported in a poster at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

The 20 patients in the series they reported on were those who failed initial stent placement out of 813 consecutive patients who underwent a percutaneous coronary intervention at Jefferson Medical College in Philadelphia.

In these 20 cases stent delivery was unsuccessful despite predilation and several other steps: substitution of a moderate-to-stiff guidewire, reattempts with a new guiding catheter or a new stent, use of a buddy wire, and in one case use of rotational atherectomy. After failed delivery, the stents were removed from their guiding catheters, saturated with Rotaglide using a 20-cc syringe, and a second delivery was immediately attempted.

Application of Rotaglide led to successful delivery for 17 of the 20 stents, reported Dr. Awar, a cardiologist at Jefferson. Angiography showed excellent anatomic results in all 17 patients. There were no major adverse coronary events or subacute stent thromboses.

All 20 patients had arteries with complex anatomy and unfavorable morphologic features: 17 (85%) had tortuous vessels, 13 (65%) had calcification, and 10 (50%) had diffuse disease (several patients had more than one feature). The target vessels included 10 left circumflex arteries, 8 right coronary arteries, and 2 left anterior descending arteries. Average patient age was 69 years, and 75% were men.

Use of Rotaglide to smooth the way for a stubborn stent had previously been reported in isolated case studies, but not in such a large series. Prior reports also have documented up to a 4% rate of failure in delivering stents to their target lesions (in this series the rate was 2.5%: 20 out of 813).

Rotaglide is sold by Boston Scientific to reduce catheter friction during rotational atherectomy.

The study was not sponsored by Boston Scientific.

PONTE VEDRA BEACH, FLA. — Now that the first thoracic-aorta endograft is on the U.S. market, a revolution has begun in managing thoracic aorta aneurysms and dissections.

“This is a big deal. Dramatic changes are taking place in managing thoracic-aorta diseases,” Alan B. Lumsden, M.D., said at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

On March 23, the Food and Drug Administration approved the Gore TAG endoprosthesis for repair of aneurysms in the descending thoracic aorta. Several additional endoprostheses are in development, and the types of patients who are candidates for receiving these devices are expanding.

Thoracic-aorta aneurysms appear to be less prevalent than abdominal-aorta aneurysms, but thoracic defects also are underdiagnosed. Current prevalence numbers are 10.4/100,000 people. The risk factors for both abdominal and thoracic aneurysms largely overlap. The incidence of thoracic aneurysms increases markedly as people age, and the incidence also seems to be increasing overall in the United States, said Dr. Lumsden, chief of the division of vascular surgery and endovascular therapy at Baylor College of Medicine in Houston.

Most patients with thoracic-aorta aneurysms are asymptomatic; the defects are picked up incidentally in chest x-rays and CT scans. The most common symptom is pain in the shoulders or back.

Like abdominal-aortic aneurysms, the risk of rupture in thoracic aneurysms rises with the size of the aneurysm. Surgical repairs usually have not been done until the aneurysm reached about 6 cm in diameter because of the high rate of surgical complications. In patients without Marfan's syndrome, an ascending thoracic aneurysm usually has been repaired when it reached 5.5 cm in diameter, and a descending thoracic aneurysm has been repaired when it reached 6.5 cm. In patients with Marfan's syndrome, the thresholds for repair have usually been scaled back by 0.5 cm.

Endovascular repair is already the treatment of choice for symptomatic patients and those with a risk of an impending rupture. But increasingly, more complicated aneurysm patients, as well as patients with uncomplicated aortic dissections, will be treated endovascularly.

Several recent reports have documented new types of surgical procedures that have “increased the landing zone” for endovascular stenting. “In the past, we were limited by the location of the celiac, subclavian, and carotid arteries, but now there are good ways to move those around,” he said.

A descending thoracic-aorta aneurysm is repaired with an endovascular stent. Courtesy Dr. Alan B. Lumsden

PONTE VEDRA BEACH, FLA. — Now that the first thoracic-aorta endograft is on the U.S. market, a revolution has begun in managing thoracic aorta aneurysms and dissections.

“This is a big deal. Dramatic changes are taking place in managing thoracic-aorta diseases,” Alan B. Lumsden, M.D., said at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

On March 23, the Food and Drug Administration approved the Gore TAG endoprosthesis for repair of aneurysms in the descending thoracic aorta. Several additional endoprostheses are in development, and the types of patients who are candidates for receiving these devices are expanding.

Thoracic-aorta aneurysms appear to be less prevalent than abdominal-aorta aneurysms, but thoracic defects also are underdiagnosed. Current prevalence numbers are 10.4/100,000 people. The risk factors for both abdominal and thoracic aneurysms largely overlap. The incidence of thoracic aneurysms increases markedly as people age, and the incidence also seems to be increasing overall in the United States, said Dr. Lumsden, chief of the division of vascular surgery and endovascular therapy at Baylor College of Medicine in Houston.

Most patients with thoracic-aorta aneurysms are asymptomatic; the defects are picked up incidentally in chest x-rays and CT scans. The most common symptom is pain in the shoulders or back.

Like abdominal-aortic aneurysms, the risk of rupture in thoracic aneurysms rises with the size of the aneurysm. Surgical repairs usually have not been done until the aneurysm reached about 6 cm in diameter because of the high rate of surgical complications. In patients without Marfan's syndrome, an ascending thoracic aneurysm usually has been repaired when it reached 5.5 cm in diameter, and a descending thoracic aneurysm has been repaired when it reached 6.5 cm. In patients with Marfan's syndrome, the thresholds for repair have usually been scaled back by 0.5 cm.

Endovascular repair is already the treatment of choice for symptomatic patients and those with a risk of an impending rupture. But increasingly, more complicated aneurysm patients, as well as patients with uncomplicated aortic dissections, will be treated endovascularly.

Several recent reports have documented new types of surgical procedures that have “increased the landing zone” for endovascular stenting. “In the past, we were limited by the location of the celiac, subclavian, and carotid arteries, but now there are good ways to move those around,” he said.

A descending thoracic-aorta aneurysm is repaired with an endovascular stent. Courtesy Dr. Alan B. Lumsden

PONTE VEDRA BEACH, FLA. — Now that the first thoracic-aorta endograft is on the U.S. market, a revolution has begun in managing thoracic aorta aneurysms and dissections.

“This is a big deal. Dramatic changes are taking place in managing thoracic-aorta diseases,” Alan B. Lumsden, M.D., said at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

On March 23, the Food and Drug Administration approved the Gore TAG endoprosthesis for repair of aneurysms in the descending thoracic aorta. Several additional endoprostheses are in development, and the types of patients who are candidates for receiving these devices are expanding.

Thoracic-aorta aneurysms appear to be less prevalent than abdominal-aorta aneurysms, but thoracic defects also are underdiagnosed. Current prevalence numbers are 10.4/100,000 people. The risk factors for both abdominal and thoracic aneurysms largely overlap. The incidence of thoracic aneurysms increases markedly as people age, and the incidence also seems to be increasing overall in the United States, said Dr. Lumsden, chief of the division of vascular surgery and endovascular therapy at Baylor College of Medicine in Houston.

Most patients with thoracic-aorta aneurysms are asymptomatic; the defects are picked up incidentally in chest x-rays and CT scans. The most common symptom is pain in the shoulders or back.

Like abdominal-aortic aneurysms, the risk of rupture in thoracic aneurysms rises with the size of the aneurysm. Surgical repairs usually have not been done until the aneurysm reached about 6 cm in diameter because of the high rate of surgical complications. In patients without Marfan's syndrome, an ascending thoracic aneurysm usually has been repaired when it reached 5.5 cm in diameter, and a descending thoracic aneurysm has been repaired when it reached 6.5 cm. In patients with Marfan's syndrome, the thresholds for repair have usually been scaled back by 0.5 cm.

Endovascular repair is already the treatment of choice for symptomatic patients and those with a risk of an impending rupture. But increasingly, more complicated aneurysm patients, as well as patients with uncomplicated aortic dissections, will be treated endovascularly.

Several recent reports have documented new types of surgical procedures that have “increased the landing zone” for endovascular stenting. “In the past, we were limited by the location of the celiac, subclavian, and carotid arteries, but now there are good ways to move those around,” he said.

A descending thoracic-aorta aneurysm is repaired with an endovascular stent. Courtesy Dr. Alan B. Lumsden

PONTE VEDRA BEACH, FLA. — Patients with critical carotid stenosis were more likely to have a stroke following carotid artery stenting than were those without critical stenosis in a study with 350 patients.

But this doesn't mean that stenting is not a good option for these patients. Although endarterectomy is also a “viable option” for patients with critical carotid stenosis, “these patients would be challenging for endarterectomy as well” because they are at high risk for stroke after any carotid intervention, David S. Lee, M.D., said at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

In the study, critical carotid stenosis was defined as a stenosis of at least 90% that also required balloon predilation before it was possible to pass an embolic-protection device through the affected coronary artery. The need for predilation “was a marker for complex lesions and complex vessel morphology,” said Dr. Lee, a cardiologist at the Cleveland Clinic Foundation.

The study involved the 350 patients in a registry of those who underwent carotid stenting with an embolic protection device during August 1999-October 2003 at the Cleveland Clinic, of whom 21 required balloon predilation of their affected coronary artery to allow passage of an embolic protection device. All 350 patients began treatment with both aspirin and a thienopyridine (either clopidogrel or ticlopidine) at least 24 hours before their carotid procedure, and with unfractionated heparin during procedure. After the procedure, aspirin and thienopyridine treatment was continued for at least 4 weeks.

The study's primary end point was the incidence of stroke within 30 days of stenting. Two strokes occurred among the 21 patients with critical carotid stenosis (9.5%), and seven occurred among the other 329 patients (2.1%), a significant difference. The two strokes in the patients with critical carotid stenosis were not secondary to the balloon predilation procedures, Dr. Lee said.

PONTE VEDRA BEACH, FLA. — Patients with critical carotid stenosis were more likely to have a stroke following carotid artery stenting than were those without critical stenosis in a study with 350 patients.

But this doesn't mean that stenting is not a good option for these patients. Although endarterectomy is also a “viable option” for patients with critical carotid stenosis, “these patients would be challenging for endarterectomy as well” because they are at high risk for stroke after any carotid intervention, David S. Lee, M.D., said at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

In the study, critical carotid stenosis was defined as a stenosis of at least 90% that also required balloon predilation before it was possible to pass an embolic-protection device through the affected coronary artery. The need for predilation “was a marker for complex lesions and complex vessel morphology,” said Dr. Lee, a cardiologist at the Cleveland Clinic Foundation.

The study involved the 350 patients in a registry of those who underwent carotid stenting with an embolic protection device during August 1999-October 2003 at the Cleveland Clinic, of whom 21 required balloon predilation of their affected coronary artery to allow passage of an embolic protection device. All 350 patients began treatment with both aspirin and a thienopyridine (either clopidogrel or ticlopidine) at least 24 hours before their carotid procedure, and with unfractionated heparin during procedure. After the procedure, aspirin and thienopyridine treatment was continued for at least 4 weeks.

The study's primary end point was the incidence of stroke within 30 days of stenting. Two strokes occurred among the 21 patients with critical carotid stenosis (9.5%), and seven occurred among the other 329 patients (2.1%), a significant difference. The two strokes in the patients with critical carotid stenosis were not secondary to the balloon predilation procedures, Dr. Lee said.

PONTE VEDRA BEACH, FLA. — Patients with critical carotid stenosis were more likely to have a stroke following carotid artery stenting than were those without critical stenosis in a study with 350 patients.

But this doesn't mean that stenting is not a good option for these patients. Although endarterectomy is also a “viable option” for patients with critical carotid stenosis, “these patients would be challenging for endarterectomy as well” because they are at high risk for stroke after any carotid intervention, David S. Lee, M.D., said at the annual meeting of the Society for Cardiovascular Angiography and Interventions.

In the study, critical carotid stenosis was defined as a stenosis of at least 90% that also required balloon predilation before it was possible to pass an embolic-protection device through the affected coronary artery. The need for predilation “was a marker for complex lesions and complex vessel morphology,” said Dr. Lee, a cardiologist at the Cleveland Clinic Foundation.

The study involved the 350 patients in a registry of those who underwent carotid stenting with an embolic protection device during August 1999-October 2003 at the Cleveland Clinic, of whom 21 required balloon predilation of their affected coronary artery to allow passage of an embolic protection device. All 350 patients began treatment with both aspirin and a thienopyridine (either clopidogrel or ticlopidine) at least 24 hours before their carotid procedure, and with unfractionated heparin during procedure. After the procedure, aspirin and thienopyridine treatment was continued for at least 4 weeks.

The study's primary end point was the incidence of stroke within 30 days of stenting. Two strokes occurred among the 21 patients with critical carotid stenosis (9.5%), and seven occurred among the other 329 patients (2.1%), a significant difference. The two strokes in the patients with critical carotid stenosis were not secondary to the balloon predilation procedures, Dr. Lee said.