Michele G. Sullivan

A 3-day course of prednisolone appears effective in Kawasaki disease patients who are unresponsive to multiple infusions of intravenous immunoglobulin, Dr. Seiichiro Takeshita reported.

Their success in treating nonresponders with prednisolone infusion suggests that IVIG-resistant patients may not require steroid pulse therapy, which has been associated with an increased risk of coronary aneurysm rupture, hypertension, seizures, and gastric erosion in this group (Clin. Pediatr. 2005;44:423–6).

Dr. Takeshita of the University of Shizuoka, Japan, and his colleagues administered 3-day courses of prednisolone every 8 hours (1–2 mg/kg per day) to six children, aged from 10 months to 9 years, who had failed to respond to repeated courses of IVIG for Kawasaki disease. Five of the children also received ulinastatin, a serine protease inhibitor not currently available in the United States.

Three patients had complications of the disease, including arthritis, myocarditis, and depressed left ventricular systolic function. All of the patients had dilated coronary arteries before prednisolone was administered. Five of the children became afebrile and had a significant decrease in C-reactive protein (CRP) levels within 24 hours of their first course of prednisolone.

The sixth patient had a persistent low-grade fever and high-CRP level after the first course, and developed a high-grade fever and high-CRP level 3 days after the first course ended. He then received a second, 3-day course of prednisolone (1.5 mg/kg per day). Within 24 hours, he became afebrile and had a significant drop in CRP level.

A 3-day course of prednisolone appears effective in Kawasaki disease patients who are unresponsive to multiple infusions of intravenous immunoglobulin, Dr. Seiichiro Takeshita reported.

Their success in treating nonresponders with prednisolone infusion suggests that IVIG-resistant patients may not require steroid pulse therapy, which has been associated with an increased risk of coronary aneurysm rupture, hypertension, seizures, and gastric erosion in this group (Clin. Pediatr. 2005;44:423–6).

Dr. Takeshita of the University of Shizuoka, Japan, and his colleagues administered 3-day courses of prednisolone every 8 hours (1–2 mg/kg per day) to six children, aged from 10 months to 9 years, who had failed to respond to repeated courses of IVIG for Kawasaki disease. Five of the children also received ulinastatin, a serine protease inhibitor not currently available in the United States.

Three patients had complications of the disease, including arthritis, myocarditis, and depressed left ventricular systolic function. All of the patients had dilated coronary arteries before prednisolone was administered. Five of the children became afebrile and had a significant decrease in C-reactive protein (CRP) levels within 24 hours of their first course of prednisolone.

The sixth patient had a persistent low-grade fever and high-CRP level after the first course, and developed a high-grade fever and high-CRP level 3 days after the first course ended. He then received a second, 3-day course of prednisolone (1.5 mg/kg per day). Within 24 hours, he became afebrile and had a significant drop in CRP level.

A 3-day course of prednisolone appears effective in Kawasaki disease patients who are unresponsive to multiple infusions of intravenous immunoglobulin, Dr. Seiichiro Takeshita reported.

Their success in treating nonresponders with prednisolone infusion suggests that IVIG-resistant patients may not require steroid pulse therapy, which has been associated with an increased risk of coronary aneurysm rupture, hypertension, seizures, and gastric erosion in this group (Clin. Pediatr. 2005;44:423–6).

Dr. Takeshita of the University of Shizuoka, Japan, and his colleagues administered 3-day courses of prednisolone every 8 hours (1–2 mg/kg per day) to six children, aged from 10 months to 9 years, who had failed to respond to repeated courses of IVIG for Kawasaki disease. Five of the children also received ulinastatin, a serine protease inhibitor not currently available in the United States.

Three patients had complications of the disease, including arthritis, myocarditis, and depressed left ventricular systolic function. All of the patients had dilated coronary arteries before prednisolone was administered. Five of the children became afebrile and had a significant decrease in C-reactive protein (CRP) levels within 24 hours of their first course of prednisolone.

The sixth patient had a persistent low-grade fever and high-CRP level after the first course, and developed a high-grade fever and high-CRP level 3 days after the first course ended. He then received a second, 3-day course of prednisolone (1.5 mg/kg per day). Within 24 hours, he became afebrile and had a significant drop in CRP level.

Early intravenous heparin improves 90-day outcomes after nonlacunar stroke, Dr. Massimo Camerlingo and colleagues concluded.

Dr. Camerlingo of Ospedali Riuniti, Bergamo, Italy, and associates randomized 418 stroke patents (mean age 71 years) to either saline or heparin initiated within 3 hours of stroke; 208 received heparin and 210 received saline. The therapies were continued for 5 days, at which time both groups received 100 mg/day oral aspirin or other anticoagulants to obtain prothrombin times of 2.0–3.0 (Stroke 2005;36:2415–20).

Compared with those receiving intravenous saline, patients who got unfractionated heparin within 3 hours of their stroke were significantly more likely to be independent 3 months later (39% vs. 29%). There were fewer deaths (35 vs. 46) but more symptomatic brain hemorrhages (13 vs. 3) and fatal brain hemorrhages (7 vs. 1) in the heparin group.

Early intravenous heparin improves 90-day outcomes after nonlacunar stroke, Dr. Massimo Camerlingo and colleagues concluded.

Dr. Camerlingo of Ospedali Riuniti, Bergamo, Italy, and associates randomized 418 stroke patents (mean age 71 years) to either saline or heparin initiated within 3 hours of stroke; 208 received heparin and 210 received saline. The therapies were continued for 5 days, at which time both groups received 100 mg/day oral aspirin or other anticoagulants to obtain prothrombin times of 2.0–3.0 (Stroke 2005;36:2415–20).

Compared with those receiving intravenous saline, patients who got unfractionated heparin within 3 hours of their stroke were significantly more likely to be independent 3 months later (39% vs. 29%). There were fewer deaths (35 vs. 46) but more symptomatic brain hemorrhages (13 vs. 3) and fatal brain hemorrhages (7 vs. 1) in the heparin group.

Early intravenous heparin improves 90-day outcomes after nonlacunar stroke, Dr. Massimo Camerlingo and colleagues concluded.

Dr. Camerlingo of Ospedali Riuniti, Bergamo, Italy, and associates randomized 418 stroke patents (mean age 71 years) to either saline or heparin initiated within 3 hours of stroke; 208 received heparin and 210 received saline. The therapies were continued for 5 days, at which time both groups received 100 mg/day oral aspirin or other anticoagulants to obtain prothrombin times of 2.0–3.0 (Stroke 2005;36:2415–20).

Compared with those receiving intravenous saline, patients who got unfractionated heparin within 3 hours of their stroke were significantly more likely to be independent 3 months later (39% vs. 29%). There were fewer deaths (35 vs. 46) but more symptomatic brain hemorrhages (13 vs. 3) and fatal brain hemorrhages (7 vs. 1) in the heparin group.

When providing parents with anticipatory guidance, less is apparently more.

Parental recall of topics discussed during a well-child visit dwindles as the number of topics increases, Dr. Shari L. Barkin and her associates reported: Parents absorb the information best when physicians limit their discussions to less than nine subjects.

“Limiting the number of topics discussed, rather than attempting to squeeze more informational content into the visit, might lead to increased retention, a necessary starting point for behavior change,” wrote Dr. Barkin of Wake Forest University, Winston-Salem, N.C., and her colleagues (Ambul. Pediatr. 2005;5:372–6).

The investigators examined provider-parent agreement and parental recall of subjects discussed during 861 well-child visits. Most of the parents surveyed were mothers (90%), and most of the mothers (59%) reported at least a high school education.

The most discussed topics were car restraints, nutrition, dental care, and reading aloud. Other topics included exercise, firearms, smoking, and media use. Most providers (454) discussed 5–8 topics; 158 covered 1–4 topics, and 249 did 9–13 topics.

Immediately after the visit, parents and providers filled out surveys about the discussions. There was good agreement (at least 70%) about what was and was not discussed, but overall, parents reported discussing slightly fewer topics than did providers (mean topics 6.33 vs. 6.9, respectively). The best agreement between parents and providers occurred when five to eight topics had been discussed. When there were fewer than five topics, parents reported having discussed more topics than providers reported; in discussions of more than nine topics, parents recalled fewer topics than providers recalled.

Parental recall dwindled with time, the investigators wrote. One month after the visit, parents who heard the fewest subjects recalled discussing more than their providers had reported post visit (mean 5.58 vs. 3.12, respectively).

Parents who heard the most topics recalled fewer topics than their providers had reported post visit (mean 8.63 vs. 10.16, respectively).

When providing parents with anticipatory guidance, less is apparently more.

Parental recall of topics discussed during a well-child visit dwindles as the number of topics increases, Dr. Shari L. Barkin and her associates reported: Parents absorb the information best when physicians limit their discussions to less than nine subjects.

“Limiting the number of topics discussed, rather than attempting to squeeze more informational content into the visit, might lead to increased retention, a necessary starting point for behavior change,” wrote Dr. Barkin of Wake Forest University, Winston-Salem, N.C., and her colleagues (Ambul. Pediatr. 2005;5:372–6).

The investigators examined provider-parent agreement and parental recall of subjects discussed during 861 well-child visits. Most of the parents surveyed were mothers (90%), and most of the mothers (59%) reported at least a high school education.

The most discussed topics were car restraints, nutrition, dental care, and reading aloud. Other topics included exercise, firearms, smoking, and media use. Most providers (454) discussed 5–8 topics; 158 covered 1–4 topics, and 249 did 9–13 topics.

Immediately after the visit, parents and providers filled out surveys about the discussions. There was good agreement (at least 70%) about what was and was not discussed, but overall, parents reported discussing slightly fewer topics than did providers (mean topics 6.33 vs. 6.9, respectively). The best agreement between parents and providers occurred when five to eight topics had been discussed. When there were fewer than five topics, parents reported having discussed more topics than providers reported; in discussions of more than nine topics, parents recalled fewer topics than providers recalled.

Parental recall dwindled with time, the investigators wrote. One month after the visit, parents who heard the fewest subjects recalled discussing more than their providers had reported post visit (mean 5.58 vs. 3.12, respectively).

Parents who heard the most topics recalled fewer topics than their providers had reported post visit (mean 8.63 vs. 10.16, respectively).

When providing parents with anticipatory guidance, less is apparently more.

Parental recall of topics discussed during a well-child visit dwindles as the number of topics increases, Dr. Shari L. Barkin and her associates reported: Parents absorb the information best when physicians limit their discussions to less than nine subjects.

“Limiting the number of topics discussed, rather than attempting to squeeze more informational content into the visit, might lead to increased retention, a necessary starting point for behavior change,” wrote Dr. Barkin of Wake Forest University, Winston-Salem, N.C., and her colleagues (Ambul. Pediatr. 2005;5:372–6).

The investigators examined provider-parent agreement and parental recall of subjects discussed during 861 well-child visits. Most of the parents surveyed were mothers (90%), and most of the mothers (59%) reported at least a high school education.

The most discussed topics were car restraints, nutrition, dental care, and reading aloud. Other topics included exercise, firearms, smoking, and media use. Most providers (454) discussed 5–8 topics; 158 covered 1–4 topics, and 249 did 9–13 topics.

Immediately after the visit, parents and providers filled out surveys about the discussions. There was good agreement (at least 70%) about what was and was not discussed, but overall, parents reported discussing slightly fewer topics than did providers (mean topics 6.33 vs. 6.9, respectively). The best agreement between parents and providers occurred when five to eight topics had been discussed. When there were fewer than five topics, parents reported having discussed more topics than providers reported; in discussions of more than nine topics, parents recalled fewer topics than providers recalled.

Parental recall dwindled with time, the investigators wrote. One month after the visit, parents who heard the fewest subjects recalled discussing more than their providers had reported post visit (mean 5.58 vs. 3.12, respectively).

Parents who heard the most topics recalled fewer topics than their providers had reported post visit (mean 8.63 vs. 10.16, respectively).

The Food and Drug Administration and GlaxoSmithKline are notifying physicians of the possibility of new onset or worsening diabetic macular edema associated with drugs containing rosiglitazone.

In a “Dear Health Care Provider” letter posted on the FDA's Medwatch Web site, the drug company said it has received “very rare” postmarketing reports of the disorder. Bernadette King, director of product communications for the company, said the reports were less than 1 in 10,000 people taking the drug.

Ms. King said the connection between the drug and the disorder is unclear. “We don't know if the macular edema is due to the drug, or due to the disease process. But we wanted to make physicians aware of these symptoms.” She said that GlaxoSmithKline has already added new safety information and a precaution in both prescribing and patient information leaflets.

Most patients who experienced macular edema also reported concurrent peripheral edema, the drug company noted. In some cases, the macular edema resolved or improved following discontinuation of the drug; in one case, the edema resolved after dose reduction.

The letter didn't give any advice about changing doses or avoiding rosiglitazone in patients with diabetic retinopathy, which often occurs along with macular edema, or in patients with risk factors for macular edema.

In Canada, however, GlaxoSmithKline and Health Canada have recommended discontinuing the drug and consulting an ophthalmologist in patients who report visual deterioration while on rosiglitazone.

A “Dear Health Care Provider” letter, distributed in late 2005 to Canadian physicians, warns that rosiglitazone “should be used with caution in patients with pre-existing diagnosis of macular edema or diabetic retinopathy.” The letter also mentions that new safety information will soon be included in the drug's leaflet.

“We are working with our other global markets to see how we can best alert prescribers to this information,” Ms. King said.

A search of PubMed identified just one published report of rosiglitazone being associated with diabetic macular edema. A 37-year-old man with type 1 diabetes, who had been taking the drug for 3 years, reported a sudden decrease in visual acuity 1 month after his dose was increased from 2 mg/day to 8 mg/day. Bilateral macular edema was present, as was peripheral edema. Three weeks after the rosiglitazone dosage was decreased to 2 mg/day, his visual acuity had improved to baseline, and the macular edema had resolved (Arch. Ophthalmol. 2005;123:1273–5).

The report's author, Dr. Michael Colucciello, an ophthalmologist in Moorestown, N.J., warned physicians prescribing rosiglitazone and other thiazolidinediones to be aware of the possibility of decreased vision associated with the development of macular edema. “Caution should be exercised when thiazolidinediones are used in those [patients] with nephropathy or congestive heart failure,” he wrote. “Options for the management of rosiglitazone- or thiazolidinedione-induced macular edema with vision loss include dose reduction and discontinuation.”

The Food and Drug Administration and GlaxoSmithKline are notifying physicians of the possibility of new onset or worsening diabetic macular edema associated with drugs containing rosiglitazone.

In a “Dear Health Care Provider” letter posted on the FDA's Medwatch Web site, the drug company said it has received “very rare” postmarketing reports of the disorder. Bernadette King, director of product communications for the company, said the reports were less than 1 in 10,000 people taking the drug.

Ms. King said the connection between the drug and the disorder is unclear. “We don't know if the macular edema is due to the drug, or due to the disease process. But we wanted to make physicians aware of these symptoms.” She said that GlaxoSmithKline has already added new safety information and a precaution in both prescribing and patient information leaflets.

Most patients who experienced macular edema also reported concurrent peripheral edema, the drug company noted. In some cases, the macular edema resolved or improved following discontinuation of the drug; in one case, the edema resolved after dose reduction.

The letter didn't give any advice about changing doses or avoiding rosiglitazone in patients with diabetic retinopathy, which often occurs along with macular edema, or in patients with risk factors for macular edema.

In Canada, however, GlaxoSmithKline and Health Canada have recommended discontinuing the drug and consulting an ophthalmologist in patients who report visual deterioration while on rosiglitazone.

A “Dear Health Care Provider” letter, distributed in late 2005 to Canadian physicians, warns that rosiglitazone “should be used with caution in patients with pre-existing diagnosis of macular edema or diabetic retinopathy.” The letter also mentions that new safety information will soon be included in the drug's leaflet.

“We are working with our other global markets to see how we can best alert prescribers to this information,” Ms. King said.

A search of PubMed identified just one published report of rosiglitazone being associated with diabetic macular edema. A 37-year-old man with type 1 diabetes, who had been taking the drug for 3 years, reported a sudden decrease in visual acuity 1 month after his dose was increased from 2 mg/day to 8 mg/day. Bilateral macular edema was present, as was peripheral edema. Three weeks after the rosiglitazone dosage was decreased to 2 mg/day, his visual acuity had improved to baseline, and the macular edema had resolved (Arch. Ophthalmol. 2005;123:1273–5).

The report's author, Dr. Michael Colucciello, an ophthalmologist in Moorestown, N.J., warned physicians prescribing rosiglitazone and other thiazolidinediones to be aware of the possibility of decreased vision associated with the development of macular edema. “Caution should be exercised when thiazolidinediones are used in those [patients] with nephropathy or congestive heart failure,” he wrote. “Options for the management of rosiglitazone- or thiazolidinedione-induced macular edema with vision loss include dose reduction and discontinuation.”

The Food and Drug Administration and GlaxoSmithKline are notifying physicians of the possibility of new onset or worsening diabetic macular edema associated with drugs containing rosiglitazone.

In a “Dear Health Care Provider” letter posted on the FDA's Medwatch Web site, the drug company said it has received “very rare” postmarketing reports of the disorder. Bernadette King, director of product communications for the company, said the reports were less than 1 in 10,000 people taking the drug.

Ms. King said the connection between the drug and the disorder is unclear. “We don't know if the macular edema is due to the drug, or due to the disease process. But we wanted to make physicians aware of these symptoms.” She said that GlaxoSmithKline has already added new safety information and a precaution in both prescribing and patient information leaflets.

Most patients who experienced macular edema also reported concurrent peripheral edema, the drug company noted. In some cases, the macular edema resolved or improved following discontinuation of the drug; in one case, the edema resolved after dose reduction.

The letter didn't give any advice about changing doses or avoiding rosiglitazone in patients with diabetic retinopathy, which often occurs along with macular edema, or in patients with risk factors for macular edema.

In Canada, however, GlaxoSmithKline and Health Canada have recommended discontinuing the drug and consulting an ophthalmologist in patients who report visual deterioration while on rosiglitazone.

A “Dear Health Care Provider” letter, distributed in late 2005 to Canadian physicians, warns that rosiglitazone “should be used with caution in patients with pre-existing diagnosis of macular edema or diabetic retinopathy.” The letter also mentions that new safety information will soon be included in the drug's leaflet.

“We are working with our other global markets to see how we can best alert prescribers to this information,” Ms. King said.

A search of PubMed identified just one published report of rosiglitazone being associated with diabetic macular edema. A 37-year-old man with type 1 diabetes, who had been taking the drug for 3 years, reported a sudden decrease in visual acuity 1 month after his dose was increased from 2 mg/day to 8 mg/day. Bilateral macular edema was present, as was peripheral edema. Three weeks after the rosiglitazone dosage was decreased to 2 mg/day, his visual acuity had improved to baseline, and the macular edema had resolved (Arch. Ophthalmol. 2005;123:1273–5).

The report's author, Dr. Michael Colucciello, an ophthalmologist in Moorestown, N.J., warned physicians prescribing rosiglitazone and other thiazolidinediones to be aware of the possibility of decreased vision associated with the development of macular edema. “Caution should be exercised when thiazolidinediones are used in those [patients] with nephropathy or congestive heart failure,” he wrote. “Options for the management of rosiglitazone- or thiazolidinedione-induced macular edema with vision loss include dose reduction and discontinuation.”

During the first year after activation of an implantable cardioverter defibrillator, a combination of amiodarone plus a β-blocker significantly reduced the risk of shock, compared with β-blocker alone or sotalol alone.

Because ICD shocks are painful and have been linked to reduced physical function and mental well-being, efforts should be made to reduce such shocks, wrote Dr. Stuart J. Connolly and associates. However, because amiodarone is associated with an increased risk of pulmonary and thyroid adverse events, “therapeutic decisions should be individualized, taking into account possible improvements in quality of life and the small, but increased, risk of drug-related adverse effects,” wrote Dr. Connolly of McMaster University, Hamilton, Ontario, and his colleagues (JAMA 2006;295:165–71).

In the Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial, the researchers randomized 412 patients with a newly implanted St. Jude Medical dual-chamber ICD for secondary prevention of serious malignant ventricular arrhythmias to either a β-blocker (138), amiodarone plus a β-blocker (140), or sotalol alone (134). Most of the patients (80%) were male; the mean age was 64 and 80% had a history of myocardial infarction.

OPTIC's primary end point was the first occurrence of any shock delivered by the ICD. Compared with a β-blocker alone, amiodarone plus β-blocker significantly reduced the risk of shock (hazard ratio 0.27). Sotalol showed a nonsignificant trend toward reduced risk (hazard ratio 0.61), compared with β-blocker alone.

During the 12-month study, there were 41 shocks in the β-blocker alone group, 26 in the sotalol group, and 12 in the amiodarone plus β-blocker group, translating to event rates of 39%, 24%, and 10%.

Amiodarone plus β-blocker significantly cut the rate of both appropriate and inappropriate shocks, with hazard ratios of 0.30 and 0.27, respectively, compared with β-blocker alone. Reductions in appropriate and inappropriate shocks with sotalol did not reach statistical significance (hazard ratios 0.65 and 0.61, respectively).

The mortality rate was low (3%/year) and did not differ significantly between groups. However, adverse events, especially pulmonary and thyroid events, were significantly higher in the amiodarone group, in which there were seven pulmonary adverse events, six cases of hypothyroidism, and two cases of hyperthyroidism. In the sotalol group, there were four pulmonary adverse events, and one case of hypothyroidism. There were no pulmonary or thyroid adverse events in the β-blocker only group.

The sotalol group had the most patients who discontinued therapy (23%). The discontinuation rate was 18% in the amiodarone group and 5% in the β-blocker group. However, the investigators noted, about 78% of patients were already on β-blockers at baseline, so this could have reduced the dropout rate in that group.

In the early days of ICDs, continuing antiarrhythmic drug therapy was usually discontinued because it “seemed redundant, akin to 'a belt plus suspenders,'” Dr. Richard L. Page wrote in an accompanying editorial. But antiarrhythmic therapy can reduce or eliminate shocks by suppressing ventricular arrhythmias or by slowing ventricular tachycardia to the extent that it can be corrected with programmed pacing.

He agreed, however, that drug therapy after ICD implantation should be individualized. In addition to adverse events, antiarrhythmic drugs can interfere with the device function by increasing, rather than decreasing, the defibrillation threshold (JAMA 2006;295:211–3).

“At present, all patients with an ICD who can tolerate such therapy should receive a β-blocker,” wrote Dr. Page of the University of Washington, Seattle. “The addition of amiodarone or substitution with sotalol cannot be advocated for all patients and should be considered on an individual basis.”

During the first year after activation of an implantable cardioverter defibrillator, a combination of amiodarone plus a β-blocker significantly reduced the risk of shock, compared with β-blocker alone or sotalol alone.

Because ICD shocks are painful and have been linked to reduced physical function and mental well-being, efforts should be made to reduce such shocks, wrote Dr. Stuart J. Connolly and associates. However, because amiodarone is associated with an increased risk of pulmonary and thyroid adverse events, “therapeutic decisions should be individualized, taking into account possible improvements in quality of life and the small, but increased, risk of drug-related adverse effects,” wrote Dr. Connolly of McMaster University, Hamilton, Ontario, and his colleagues (JAMA 2006;295:165–71).

In the Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial, the researchers randomized 412 patients with a newly implanted St. Jude Medical dual-chamber ICD for secondary prevention of serious malignant ventricular arrhythmias to either a β-blocker (138), amiodarone plus a β-blocker (140), or sotalol alone (134). Most of the patients (80%) were male; the mean age was 64 and 80% had a history of myocardial infarction.

OPTIC's primary end point was the first occurrence of any shock delivered by the ICD. Compared with a β-blocker alone, amiodarone plus β-blocker significantly reduced the risk of shock (hazard ratio 0.27). Sotalol showed a nonsignificant trend toward reduced risk (hazard ratio 0.61), compared with β-blocker alone.

During the 12-month study, there were 41 shocks in the β-blocker alone group, 26 in the sotalol group, and 12 in the amiodarone plus β-blocker group, translating to event rates of 39%, 24%, and 10%.

Amiodarone plus β-blocker significantly cut the rate of both appropriate and inappropriate shocks, with hazard ratios of 0.30 and 0.27, respectively, compared with β-blocker alone. Reductions in appropriate and inappropriate shocks with sotalol did not reach statistical significance (hazard ratios 0.65 and 0.61, respectively).

The mortality rate was low (3%/year) and did not differ significantly between groups. However, adverse events, especially pulmonary and thyroid events, were significantly higher in the amiodarone group, in which there were seven pulmonary adverse events, six cases of hypothyroidism, and two cases of hyperthyroidism. In the sotalol group, there were four pulmonary adverse events, and one case of hypothyroidism. There were no pulmonary or thyroid adverse events in the β-blocker only group.

The sotalol group had the most patients who discontinued therapy (23%). The discontinuation rate was 18% in the amiodarone group and 5% in the β-blocker group. However, the investigators noted, about 78% of patients were already on β-blockers at baseline, so this could have reduced the dropout rate in that group.

In the early days of ICDs, continuing antiarrhythmic drug therapy was usually discontinued because it “seemed redundant, akin to 'a belt plus suspenders,'” Dr. Richard L. Page wrote in an accompanying editorial. But antiarrhythmic therapy can reduce or eliminate shocks by suppressing ventricular arrhythmias or by slowing ventricular tachycardia to the extent that it can be corrected with programmed pacing.

He agreed, however, that drug therapy after ICD implantation should be individualized. In addition to adverse events, antiarrhythmic drugs can interfere with the device function by increasing, rather than decreasing, the defibrillation threshold (JAMA 2006;295:211–3).

“At present, all patients with an ICD who can tolerate such therapy should receive a β-blocker,” wrote Dr. Page of the University of Washington, Seattle. “The addition of amiodarone or substitution with sotalol cannot be advocated for all patients and should be considered on an individual basis.”

During the first year after activation of an implantable cardioverter defibrillator, a combination of amiodarone plus a β-blocker significantly reduced the risk of shock, compared with β-blocker alone or sotalol alone.

Because ICD shocks are painful and have been linked to reduced physical function and mental well-being, efforts should be made to reduce such shocks, wrote Dr. Stuart J. Connolly and associates. However, because amiodarone is associated with an increased risk of pulmonary and thyroid adverse events, “therapeutic decisions should be individualized, taking into account possible improvements in quality of life and the small, but increased, risk of drug-related adverse effects,” wrote Dr. Connolly of McMaster University, Hamilton, Ontario, and his colleagues (JAMA 2006;295:165–71).

In the Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial, the researchers randomized 412 patients with a newly implanted St. Jude Medical dual-chamber ICD for secondary prevention of serious malignant ventricular arrhythmias to either a β-blocker (138), amiodarone plus a β-blocker (140), or sotalol alone (134). Most of the patients (80%) were male; the mean age was 64 and 80% had a history of myocardial infarction.

OPTIC's primary end point was the first occurrence of any shock delivered by the ICD. Compared with a β-blocker alone, amiodarone plus β-blocker significantly reduced the risk of shock (hazard ratio 0.27). Sotalol showed a nonsignificant trend toward reduced risk (hazard ratio 0.61), compared with β-blocker alone.

During the 12-month study, there were 41 shocks in the β-blocker alone group, 26 in the sotalol group, and 12 in the amiodarone plus β-blocker group, translating to event rates of 39%, 24%, and 10%.

Amiodarone plus β-blocker significantly cut the rate of both appropriate and inappropriate shocks, with hazard ratios of 0.30 and 0.27, respectively, compared with β-blocker alone. Reductions in appropriate and inappropriate shocks with sotalol did not reach statistical significance (hazard ratios 0.65 and 0.61, respectively).

The mortality rate was low (3%/year) and did not differ significantly between groups. However, adverse events, especially pulmonary and thyroid events, were significantly higher in the amiodarone group, in which there were seven pulmonary adverse events, six cases of hypothyroidism, and two cases of hyperthyroidism. In the sotalol group, there were four pulmonary adverse events, and one case of hypothyroidism. There were no pulmonary or thyroid adverse events in the β-blocker only group.

The sotalol group had the most patients who discontinued therapy (23%). The discontinuation rate was 18% in the amiodarone group and 5% in the β-blocker group. However, the investigators noted, about 78% of patients were already on β-blockers at baseline, so this could have reduced the dropout rate in that group.

In the early days of ICDs, continuing antiarrhythmic drug therapy was usually discontinued because it “seemed redundant, akin to 'a belt plus suspenders,'” Dr. Richard L. Page wrote in an accompanying editorial. But antiarrhythmic therapy can reduce or eliminate shocks by suppressing ventricular arrhythmias or by slowing ventricular tachycardia to the extent that it can be corrected with programmed pacing.

He agreed, however, that drug therapy after ICD implantation should be individualized. In addition to adverse events, antiarrhythmic drugs can interfere with the device function by increasing, rather than decreasing, the defibrillation threshold (JAMA 2006;295:211–3).

“At present, all patients with an ICD who can tolerate such therapy should receive a β-blocker,” wrote Dr. Page of the University of Washington, Seattle. “The addition of amiodarone or substitution with sotalol cannot be advocated for all patients and should be considered on an individual basis.”

For every hour an acute ischemic stroke is untreated, the human forebrain loses 120 million neurons, 830 billion synapses, and 447 miles of myelinated fiber–the equivalent of 3.6 years of normal aging.

The numbers lend a new urgency to the phrase “time is brain,” said Dr. Jeffrey Saver, who created the quantitative analysis of neural death in stroke (Stroke 2006;37:263–6).

“The figures stagger and motivate,” wrote Dr. Saver of the University of California, Los Angeles Stroke Center. “For patients experiencing acute ischemic stroke, and for the physicians [and others] treating them, every second counts.”

Dr. Saver used an extensive literature review to estimate total counts for neurons, synapses, and myelinated fiber length in the forebrain.

He then used published data to estimate the impact of the duration of infarct growth, infarct volume, and time to treatment on these structures.

He concluded that the forebrain contains an average of 22 billion neurons, 157 trillion synapses, and 84,500 miles of myelinated fibers. The accepted estimate for the rate of neuronal loss in the neocortex alone (which is 86% of the forebrain) is about 31 million per year during normal aging, he said.

The impact of an untreated large vessel ischemic stroke is sudden and severe. Every untreated minute results in the loss of 2 million neurons, 14 billion synapses, and 7.5 miles of myelinated fibers, Dr. Saver said. On a per-second basis, the damage is 32,000 neurons, 230 million synapses, and 218 yards of myelinated fiber. Thus, such a stroke, at an average duration of 10 hours, can age the brain 36 years, destroying 1.2 billion neurons, 8.3 trillion synapses, and 4,470 miles of myelinated fibers.

In an accompanying editorial, Dr. Steven R. Levine suggested that transient ischemic attacks might actually be microstrokes that inflict permanent–although clinically undetectable–neural damage.

“Even after a few seconds of the focal cerebral ischemic process, tens of thousands of neurons and hundreds of millions of synapses are lost–if the time function is linear,” said Dr. Levine of Mount Sinai School of Medicine, New York.

Dr. Levine suggested that the unanswered clinical question then becomes: “Are these very brief episodes then really 'microstrokes' invisible to the neurological examination or current imaging modalities, with very subtle, if any, detectable parenchymal or functional change?” (Stroke 2006;37:10).

For every hour an acute ischemic stroke is untreated, the human forebrain loses 120 million neurons, 830 billion synapses, and 447 miles of myelinated fiber–the equivalent of 3.6 years of normal aging.

The numbers lend a new urgency to the phrase “time is brain,” said Dr. Jeffrey Saver, who created the quantitative analysis of neural death in stroke (Stroke 2006;37:263–6).

“The figures stagger and motivate,” wrote Dr. Saver of the University of California, Los Angeles Stroke Center. “For patients experiencing acute ischemic stroke, and for the physicians [and others] treating them, every second counts.”

Dr. Saver used an extensive literature review to estimate total counts for neurons, synapses, and myelinated fiber length in the forebrain.

He then used published data to estimate the impact of the duration of infarct growth, infarct volume, and time to treatment on these structures.

He concluded that the forebrain contains an average of 22 billion neurons, 157 trillion synapses, and 84,500 miles of myelinated fibers. The accepted estimate for the rate of neuronal loss in the neocortex alone (which is 86% of the forebrain) is about 31 million per year during normal aging, he said.

The impact of an untreated large vessel ischemic stroke is sudden and severe. Every untreated minute results in the loss of 2 million neurons, 14 billion synapses, and 7.5 miles of myelinated fibers, Dr. Saver said. On a per-second basis, the damage is 32,000 neurons, 230 million synapses, and 218 yards of myelinated fiber. Thus, such a stroke, at an average duration of 10 hours, can age the brain 36 years, destroying 1.2 billion neurons, 8.3 trillion synapses, and 4,470 miles of myelinated fibers.

In an accompanying editorial, Dr. Steven R. Levine suggested that transient ischemic attacks might actually be microstrokes that inflict permanent–although clinically undetectable–neural damage.

“Even after a few seconds of the focal cerebral ischemic process, tens of thousands of neurons and hundreds of millions of synapses are lost–if the time function is linear,” said Dr. Levine of Mount Sinai School of Medicine, New York.

Dr. Levine suggested that the unanswered clinical question then becomes: “Are these very brief episodes then really 'microstrokes' invisible to the neurological examination or current imaging modalities, with very subtle, if any, detectable parenchymal or functional change?” (Stroke 2006;37:10).

For every hour an acute ischemic stroke is untreated, the human forebrain loses 120 million neurons, 830 billion synapses, and 447 miles of myelinated fiber–the equivalent of 3.6 years of normal aging.

The numbers lend a new urgency to the phrase “time is brain,” said Dr. Jeffrey Saver, who created the quantitative analysis of neural death in stroke (Stroke 2006;37:263–6).

“The figures stagger and motivate,” wrote Dr. Saver of the University of California, Los Angeles Stroke Center. “For patients experiencing acute ischemic stroke, and for the physicians [and others] treating them, every second counts.”

Dr. Saver used an extensive literature review to estimate total counts for neurons, synapses, and myelinated fiber length in the forebrain.

He then used published data to estimate the impact of the duration of infarct growth, infarct volume, and time to treatment on these structures.

He concluded that the forebrain contains an average of 22 billion neurons, 157 trillion synapses, and 84,500 miles of myelinated fibers. The accepted estimate for the rate of neuronal loss in the neocortex alone (which is 86% of the forebrain) is about 31 million per year during normal aging, he said.

The impact of an untreated large vessel ischemic stroke is sudden and severe. Every untreated minute results in the loss of 2 million neurons, 14 billion synapses, and 7.5 miles of myelinated fibers, Dr. Saver said. On a per-second basis, the damage is 32,000 neurons, 230 million synapses, and 218 yards of myelinated fiber. Thus, such a stroke, at an average duration of 10 hours, can age the brain 36 years, destroying 1.2 billion neurons, 8.3 trillion synapses, and 4,470 miles of myelinated fibers.

In an accompanying editorial, Dr. Steven R. Levine suggested that transient ischemic attacks might actually be microstrokes that inflict permanent–although clinically undetectable–neural damage.

“Even after a few seconds of the focal cerebral ischemic process, tens of thousands of neurons and hundreds of millions of synapses are lost–if the time function is linear,” said Dr. Levine of Mount Sinai School of Medicine, New York.

Dr. Levine suggested that the unanswered clinical question then becomes: “Are these very brief episodes then really 'microstrokes' invisible to the neurological examination or current imaging modalities, with very subtle, if any, detectable parenchymal or functional change?” (Stroke 2006;37:10).

TORONTO – Some symptoms associated with autism–including hyperactivity, inattention, stereotypy, and aggression–can be improved with pharmacotherapy, Dr. Christopher McDougle said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

But treating impaired social relatedness remains challenging, said Dr. McDougle of Indiana University, Indianapolis.

Nothing has been conclusively shown to be effective, although SSRIs, atypical antipsychotics, cholinergic agents, and glutamatergic agents have shown some promise, according to Dr. McDougle.

“We have seen some hints of effectiveness in some studies, and we're more optimistic about them,” he said. “They deserve further study.”

The psychostimulants have not fared well in autism, said Dr. McDougle, chairman and professor of psychiatry at the university. “There were substantial activating side effects in the early trials, and tolerability often remains an issue.”

He and his colleagues are about to publish results from a study of methylphenidate in children with pervasive developmental disorder (PDD) and hyperactivity. The 72 children received placebo and three doses of the drug in random order. Although 44 children responded to the drug, 13 (18%) dropped out because they couldn't tolerate at least two doses of it. Irritability was the most frequent cause of discontinuation.

“Right away, we got a sense tolerance was a concern, and the global response rate was much less than we see with typical children with ADHD,” Dr. McDougle said. Increased social withdrawal also occurred in some of the children. “Sometimes psychostimulants can lead to social withdrawal in ADHD, and at the highest doses in PDD, we saw a worsening of withdrawal.” Treating inattention in PDD is very difficult, Dr. McDougle said. “There are probably multiple causes for inattention. We really don't know what is going on,” he explained.

Unpublished data collected by Dr. David Posey, also of Indiana University, and his colleagues suggest that atomoxetine (Straterra) might be useful for inattention and hyperactivity in PDD.

Dr. Posey's open-label study included 16 drug-free children with PDD who received a mean dose of 1.2 mg/kg per day. The results were robust, Dr. McDougle said, with 75% of patients much or very much improved. However, two children (16%) were rated as much worse because of increased irritability. “The results are encouraging but preliminary,” Dr. McDougle said. “It's a possible alternative for those who can't tolerate a stimulant.”

Guanfacine (Tenex), generally used to treat high blood pressure, may be the best first step in pharmacotherapy for inattention, he said. “It might not help, but it won't make them worse. It may be the first use of these medications for the family, and you don't want to get off on the wrong foot by giving them a bad experience. But the best response is with a stimulant, if you can match up the right patient.”

Clonidine, an antihypertensive agent, has been shown effective in two small placebo-controlled studies. But that effectiveness may be partly attributable to the drug's sedative effects, he noted.

SSRIs are being studied for repetitive behavior, because they are often found in obsessive-compulsive disorder. Serotonin abnormalities are also found in autism, Dr. McDougle said.

Fluoxetine has been the most successful of these drugs, he said. A 2005 crossover placebo-controlled study of 39 children (aged 5–16 years) showed a significant reduction in repetitive behaviors with the drug. No significant effects on speech or social interaction were found, and no differences were found in side effects between the drug and placebo (Neuropsychopharmacology 2005;30:582–9). But parents should think carefully before medicating children just to reduce these behaviors, he said.

“You don't need to eliminate it just because it's present,” Dr. McDougle said. “Maybe it's OK to do these things if you have autism. Maybe you can just learn to leave it alone and appreciate the child for his uniqueness.”

Treating inattention in pervasive developmental disorder is very difficult. DR. MCDOUGLE

TORONTO – Some symptoms associated with autism–including hyperactivity, inattention, stereotypy, and aggression–can be improved with pharmacotherapy, Dr. Christopher McDougle said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

But treating impaired social relatedness remains challenging, said Dr. McDougle of Indiana University, Indianapolis.

Nothing has been conclusively shown to be effective, although SSRIs, atypical antipsychotics, cholinergic agents, and glutamatergic agents have shown some promise, according to Dr. McDougle.

“We have seen some hints of effectiveness in some studies, and we're more optimistic about them,” he said. “They deserve further study.”

The psychostimulants have not fared well in autism, said Dr. McDougle, chairman and professor of psychiatry at the university. “There were substantial activating side effects in the early trials, and tolerability often remains an issue.”

He and his colleagues are about to publish results from a study of methylphenidate in children with pervasive developmental disorder (PDD) and hyperactivity. The 72 children received placebo and three doses of the drug in random order. Although 44 children responded to the drug, 13 (18%) dropped out because they couldn't tolerate at least two doses of it. Irritability was the most frequent cause of discontinuation.

“Right away, we got a sense tolerance was a concern, and the global response rate was much less than we see with typical children with ADHD,” Dr. McDougle said. Increased social withdrawal also occurred in some of the children. “Sometimes psychostimulants can lead to social withdrawal in ADHD, and at the highest doses in PDD, we saw a worsening of withdrawal.” Treating inattention in PDD is very difficult, Dr. McDougle said. “There are probably multiple causes for inattention. We really don't know what is going on,” he explained.

Unpublished data collected by Dr. David Posey, also of Indiana University, and his colleagues suggest that atomoxetine (Straterra) might be useful for inattention and hyperactivity in PDD.

Dr. Posey's open-label study included 16 drug-free children with PDD who received a mean dose of 1.2 mg/kg per day. The results were robust, Dr. McDougle said, with 75% of patients much or very much improved. However, two children (16%) were rated as much worse because of increased irritability. “The results are encouraging but preliminary,” Dr. McDougle said. “It's a possible alternative for those who can't tolerate a stimulant.”

Guanfacine (Tenex), generally used to treat high blood pressure, may be the best first step in pharmacotherapy for inattention, he said. “It might not help, but it won't make them worse. It may be the first use of these medications for the family, and you don't want to get off on the wrong foot by giving them a bad experience. But the best response is with a stimulant, if you can match up the right patient.”

Clonidine, an antihypertensive agent, has been shown effective in two small placebo-controlled studies. But that effectiveness may be partly attributable to the drug's sedative effects, he noted.

SSRIs are being studied for repetitive behavior, because they are often found in obsessive-compulsive disorder. Serotonin abnormalities are also found in autism, Dr. McDougle said.

Fluoxetine has been the most successful of these drugs, he said. A 2005 crossover placebo-controlled study of 39 children (aged 5–16 years) showed a significant reduction in repetitive behaviors with the drug. No significant effects on speech or social interaction were found, and no differences were found in side effects between the drug and placebo (Neuropsychopharmacology 2005;30:582–9). But parents should think carefully before medicating children just to reduce these behaviors, he said.

“You don't need to eliminate it just because it's present,” Dr. McDougle said. “Maybe it's OK to do these things if you have autism. Maybe you can just learn to leave it alone and appreciate the child for his uniqueness.”

Treating inattention in pervasive developmental disorder is very difficult. DR. MCDOUGLE

TORONTO – Some symptoms associated with autism–including hyperactivity, inattention, stereotypy, and aggression–can be improved with pharmacotherapy, Dr. Christopher McDougle said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

But treating impaired social relatedness remains challenging, said Dr. McDougle of Indiana University, Indianapolis.

Nothing has been conclusively shown to be effective, although SSRIs, atypical antipsychotics, cholinergic agents, and glutamatergic agents have shown some promise, according to Dr. McDougle.

“We have seen some hints of effectiveness in some studies, and we're more optimistic about them,” he said. “They deserve further study.”

The psychostimulants have not fared well in autism, said Dr. McDougle, chairman and professor of psychiatry at the university. “There were substantial activating side effects in the early trials, and tolerability often remains an issue.”

He and his colleagues are about to publish results from a study of methylphenidate in children with pervasive developmental disorder (PDD) and hyperactivity. The 72 children received placebo and three doses of the drug in random order. Although 44 children responded to the drug, 13 (18%) dropped out because they couldn't tolerate at least two doses of it. Irritability was the most frequent cause of discontinuation.

“Right away, we got a sense tolerance was a concern, and the global response rate was much less than we see with typical children with ADHD,” Dr. McDougle said. Increased social withdrawal also occurred in some of the children. “Sometimes psychostimulants can lead to social withdrawal in ADHD, and at the highest doses in PDD, we saw a worsening of withdrawal.” Treating inattention in PDD is very difficult, Dr. McDougle said. “There are probably multiple causes for inattention. We really don't know what is going on,” he explained.

Unpublished data collected by Dr. David Posey, also of Indiana University, and his colleagues suggest that atomoxetine (Straterra) might be useful for inattention and hyperactivity in PDD.

Dr. Posey's open-label study included 16 drug-free children with PDD who received a mean dose of 1.2 mg/kg per day. The results were robust, Dr. McDougle said, with 75% of patients much or very much improved. However, two children (16%) were rated as much worse because of increased irritability. “The results are encouraging but preliminary,” Dr. McDougle said. “It's a possible alternative for those who can't tolerate a stimulant.”

Guanfacine (Tenex), generally used to treat high blood pressure, may be the best first step in pharmacotherapy for inattention, he said. “It might not help, but it won't make them worse. It may be the first use of these medications for the family, and you don't want to get off on the wrong foot by giving them a bad experience. But the best response is with a stimulant, if you can match up the right patient.”

Clonidine, an antihypertensive agent, has been shown effective in two small placebo-controlled studies. But that effectiveness may be partly attributable to the drug's sedative effects, he noted.

SSRIs are being studied for repetitive behavior, because they are often found in obsessive-compulsive disorder. Serotonin abnormalities are also found in autism, Dr. McDougle said.

Fluoxetine has been the most successful of these drugs, he said. A 2005 crossover placebo-controlled study of 39 children (aged 5–16 years) showed a significant reduction in repetitive behaviors with the drug. No significant effects on speech or social interaction were found, and no differences were found in side effects between the drug and placebo (Neuropsychopharmacology 2005;30:582–9). But parents should think carefully before medicating children just to reduce these behaviors, he said.

“You don't need to eliminate it just because it's present,” Dr. McDougle said. “Maybe it's OK to do these things if you have autism. Maybe you can just learn to leave it alone and appreciate the child for his uniqueness.”

Treating inattention in pervasive developmental disorder is very difficult. DR. MCDOUGLE

TORONTO – Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder, decreasing symptom scores twice as much as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.

The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6–17 years. Two of the studies were identical 9-week flexible-dosing trials. The third was a 7-week fixed-dose placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.

Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).

The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.

There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.

The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. The effects were consistent whether assessed by physician, parent, or teacher.

Physicians assessed almost 50% of the active groups as much improved at the end of treatment, compared with 20% of the placebo group.

Parents and teachers rated symptom improvement of those in the active group at about twice that of the placebo group in all areas: oppositional behavior, inattention, and hyperactivity.

Symptom improvement differed significantly from placebo at week 2 of treatment and continued to diverge throughout the course of all three studies.

TORONTO – Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder, decreasing symptom scores twice as much as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.

The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6–17 years. Two of the studies were identical 9-week flexible-dosing trials. The third was a 7-week fixed-dose placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.

Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).

The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.

There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.

The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. The effects were consistent whether assessed by physician, parent, or teacher.

Physicians assessed almost 50% of the active groups as much improved at the end of treatment, compared with 20% of the placebo group.

Parents and teachers rated symptom improvement of those in the active group at about twice that of the placebo group in all areas: oppositional behavior, inattention, and hyperactivity.

Symptom improvement differed significantly from placebo at week 2 of treatment and continued to diverge throughout the course of all three studies.

TORONTO – Modafinil is safe and effective in treating pediatric attention-deficit hyperactivity disorder, decreasing symptom scores twice as much as placebo, according to two posters presented at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

The posters, sponsored by Cephalon Inc., concluded that children tolerated the film-coated tablets well in dosages of up to 425 mg/day. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Those adverse events typically occurred during the first 2 weeks of therapy and decreased thereafter, said Dr. Christopher Kratochvil of the University of Nebraska.

The posters analyzed three multicenter, double-blind studies that included a total of 633 children aged 6–17 years. Two of the studies were identical 9-week flexible-dosing trials. The third was a 7-week fixed-dose placebo-controlled study (340 or 425 mg/day), followed by a 2-week period in which half the modafinil group was switched to placebo without tapering while the other half continued modafinil treatment.

Adverse events were more common in the active group than the placebo group and included insomnia (27% vs. 4%), headache (20% vs. 13%), and decreased appetite (16% vs. 3%).

The adverse events were all classified as mild to moderate. They peaked in the first 2 weeks of treatment and subsequently subsided. No apparent association was found between adverse events and dosage.

There were no significant changes in heart rate or blood pressure between the groups, and the abrupt discontinuation of the drug did not lead to acute withdrawal symptoms or rebound effects.

The drug effectively reduced the symptoms of ADHD, especially hyperactivity and inattention, reported Dr. Joseph Biederman of Massachusetts General Hospital. The effects were consistent whether assessed by physician, parent, or teacher.

Physicians assessed almost 50% of the active groups as much improved at the end of treatment, compared with 20% of the placebo group.

Parents and teachers rated symptom improvement of those in the active group at about twice that of the placebo group in all areas: oppositional behavior, inattention, and hyperactivity.

Symptom improvement differed significantly from placebo at week 2 of treatment and continued to diverge throughout the course of all three studies.

TORONTO – Reducing the dose of atomoxetine may be possible for children with attention-deficit hyperactivity disorder who have responded well to the medication, Dr. Jeffrey Newcorn reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Dr. Newcorn, of the Mount Sinai Medical Center, New York, investigated low-dose response rates in 229 children aged 6–16 years who had responded well to atomoxetine (Strattera) doses of up to 1.8 mg/kg per day in a previous trial. These children were randomized to continue their same dose of atomoxetine (mean 1.43 mg/kg per day) or to take a reduced dose (mean 0.46 mg/kg per day), and were followed for up to 8 months.

Only three children in the previous-dose group (2.6%) and three (2.5%) in the low-dose group relapsed. However, significantly more children in the low-dose group were no longer considered medication responders; i.e., they no longer had a symptom reduction of at least 40%. The rates of nonresponders were 17% (20/115) in the previous-dose group and 23% (25/109) in the low-dose group.

Tolerability was not a major issue in the study, Dr. Newcorn wrote, although adverse events were less common in the low-dose group. Headache was the most common adverse event, experienced by 21% and 16%, respectively.

“These data suggest that it is possible to maintain initial treatment gains at lower doses during continuing treatment,” he wrote. “However, they do not provide definitive evidence that the dose should be lowered during continued treatment.”

Still, he said, “The option of lowering the dose during maintenance therapy may be important for patients who respond well to initial treatment but who experience troublesome side effects.”

Dr. Newcorn is a consultant for Eli Lilly & Co., which funded the research.

TORONTO – Reducing the dose of atomoxetine may be possible for children with attention-deficit hyperactivity disorder who have responded well to the medication, Dr. Jeffrey Newcorn reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Dr. Newcorn, of the Mount Sinai Medical Center, New York, investigated low-dose response rates in 229 children aged 6–16 years who had responded well to atomoxetine (Strattera) doses of up to 1.8 mg/kg per day in a previous trial. These children were randomized to continue their same dose of atomoxetine (mean 1.43 mg/kg per day) or to take a reduced dose (mean 0.46 mg/kg per day), and were followed for up to 8 months.

Only three children in the previous-dose group (2.6%) and three (2.5%) in the low-dose group relapsed. However, significantly more children in the low-dose group were no longer considered medication responders; i.e., they no longer had a symptom reduction of at least 40%. The rates of nonresponders were 17% (20/115) in the previous-dose group and 23% (25/109) in the low-dose group.

Tolerability was not a major issue in the study, Dr. Newcorn wrote, although adverse events were less common in the low-dose group. Headache was the most common adverse event, experienced by 21% and 16%, respectively.

“These data suggest that it is possible to maintain initial treatment gains at lower doses during continuing treatment,” he wrote. “However, they do not provide definitive evidence that the dose should be lowered during continued treatment.”

Still, he said, “The option of lowering the dose during maintenance therapy may be important for patients who respond well to initial treatment but who experience troublesome side effects.”

Dr. Newcorn is a consultant for Eli Lilly & Co., which funded the research.

TORONTO – Reducing the dose of atomoxetine may be possible for children with attention-deficit hyperactivity disorder who have responded well to the medication, Dr. Jeffrey Newcorn reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Dr. Newcorn, of the Mount Sinai Medical Center, New York, investigated low-dose response rates in 229 children aged 6–16 years who had responded well to atomoxetine (Strattera) doses of up to 1.8 mg/kg per day in a previous trial. These children were randomized to continue their same dose of atomoxetine (mean 1.43 mg/kg per day) or to take a reduced dose (mean 0.46 mg/kg per day), and were followed for up to 8 months.

Only three children in the previous-dose group (2.6%) and three (2.5%) in the low-dose group relapsed. However, significantly more children in the low-dose group were no longer considered medication responders; i.e., they no longer had a symptom reduction of at least 40%. The rates of nonresponders were 17% (20/115) in the previous-dose group and 23% (25/109) in the low-dose group.

Tolerability was not a major issue in the study, Dr. Newcorn wrote, although adverse events were less common in the low-dose group. Headache was the most common adverse event, experienced by 21% and 16%, respectively.

“These data suggest that it is possible to maintain initial treatment gains at lower doses during continuing treatment,” he wrote. “However, they do not provide definitive evidence that the dose should be lowered during continued treatment.”

Still, he said, “The option of lowering the dose during maintenance therapy may be important for patients who respond well to initial treatment but who experience troublesome side effects.”

Dr. Newcorn is a consultant for Eli Lilly & Co., which funded the research.

TORONTO – Children with attention-deficit hyperactivity disorder can be successfully cross-tapered from a stimulant to atomoxetine with significant improvements in their ADHD symptoms, Dr. Humberto Quintana reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Switching from a stimulant to the serotonin norepinephrine reuptake inhibitor atomoxetine also was safe, said Dr. Quintana of the Louisiana State University Health Sciences Center, New Orleans. The study found slight, but statistically significant, increases in blood pressure and heart rate, but the safety findings otherwise were unremarkable.

The study, funded by Eli Lilly & Co.–for whom Dr. Quintana is an investigator–included 62 children aged 6–17 years. Just over half of the children (53%) were switching to atomoxetine because of inadequate response to their current medication; the rest (47%) switched because of adverse events.

Slightly more of the group (52%) were taking methylphenidate at baseline; the rest were taking an amphetamine.

During the first week of the transition period, patients received the full dose of their current medication daily, plus 0.5 mg/kg per day of atomoxetine. During the second week, they received a half-dose of their stimulant each day, plus 1.2 mg/kg per day of atomoxetine. During the final 5 weeks of the study, the patients received 1.2 mg/kg per day of atomoxetine and no stimulant.

At the end of the study, patients experienced a significant decrease in ADHD symptoms as reported by parents on the ADHD Rating Scale. The mean total score decreased from 32 to 22.5, the inattention score decreased from a mean of 17 to a mean of 13.5, and the mean hyperactivity score decreased from 13 to 9.

Most of the children (65.5%) said they preferred atomoxetine over their previous stimulant medication. When surveyed after the study, parents clearly preferred atomoxetine. Parents said they were satisfied with the drug's effect overall, as well as with its effect in both morning and evening hours. They were very satisfied with the drug's ability to “allow the child to be himself” during treatment.

Significant increases in blood pressure and heart rate were found for most of the 62 children; 53 experienced an average increase of 2.4 mm Hg in both diastolic and systolic blood pressure. Fifty-seven children experienced an average increase in heart rate of 9 beats per minute. There were no other ECG changes, including in the QT interval.

TORONTO – Children with attention-deficit hyperactivity disorder can be successfully cross-tapered from a stimulant to atomoxetine with significant improvements in their ADHD symptoms, Dr. Humberto Quintana reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Switching from a stimulant to the serotonin norepinephrine reuptake inhibitor atomoxetine also was safe, said Dr. Quintana of the Louisiana State University Health Sciences Center, New Orleans. The study found slight, but statistically significant, increases in blood pressure and heart rate, but the safety findings otherwise were unremarkable.

The study, funded by Eli Lilly & Co.–for whom Dr. Quintana is an investigator–included 62 children aged 6–17 years. Just over half of the children (53%) were switching to atomoxetine because of inadequate response to their current medication; the rest (47%) switched because of adverse events.

Slightly more of the group (52%) were taking methylphenidate at baseline; the rest were taking an amphetamine.

During the first week of the transition period, patients received the full dose of their current medication daily, plus 0.5 mg/kg per day of atomoxetine. During the second week, they received a half-dose of their stimulant each day, plus 1.2 mg/kg per day of atomoxetine. During the final 5 weeks of the study, the patients received 1.2 mg/kg per day of atomoxetine and no stimulant.

At the end of the study, patients experienced a significant decrease in ADHD symptoms as reported by parents on the ADHD Rating Scale. The mean total score decreased from 32 to 22.5, the inattention score decreased from a mean of 17 to a mean of 13.5, and the mean hyperactivity score decreased from 13 to 9.

Most of the children (65.5%) said they preferred atomoxetine over their previous stimulant medication. When surveyed after the study, parents clearly preferred atomoxetine. Parents said they were satisfied with the drug's effect overall, as well as with its effect in both morning and evening hours. They were very satisfied with the drug's ability to “allow the child to be himself” during treatment.

Significant increases in blood pressure and heart rate were found for most of the 62 children; 53 experienced an average increase of 2.4 mm Hg in both diastolic and systolic blood pressure. Fifty-seven children experienced an average increase in heart rate of 9 beats per minute. There were no other ECG changes, including in the QT interval.

TORONTO – Children with attention-deficit hyperactivity disorder can be successfully cross-tapered from a stimulant to atomoxetine with significant improvements in their ADHD symptoms, Dr. Humberto Quintana reported in a poster at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.

Switching from a stimulant to the serotonin norepinephrine reuptake inhibitor atomoxetine also was safe, said Dr. Quintana of the Louisiana State University Health Sciences Center, New Orleans. The study found slight, but statistically significant, increases in blood pressure and heart rate, but the safety findings otherwise were unremarkable.

The study, funded by Eli Lilly & Co.–for whom Dr. Quintana is an investigator–included 62 children aged 6–17 years. Just over half of the children (53%) were switching to atomoxetine because of inadequate response to their current medication; the rest (47%) switched because of adverse events.

Slightly more of the group (52%) were taking methylphenidate at baseline; the rest were taking an amphetamine.

During the first week of the transition period, patients received the full dose of their current medication daily, plus 0.5 mg/kg per day of atomoxetine. During the second week, they received a half-dose of their stimulant each day, plus 1.2 mg/kg per day of atomoxetine. During the final 5 weeks of the study, the patients received 1.2 mg/kg per day of atomoxetine and no stimulant.

At the end of the study, patients experienced a significant decrease in ADHD symptoms as reported by parents on the ADHD Rating Scale. The mean total score decreased from 32 to 22.5, the inattention score decreased from a mean of 17 to a mean of 13.5, and the mean hyperactivity score decreased from 13 to 9.

Most of the children (65.5%) said they preferred atomoxetine over their previous stimulant medication. When surveyed after the study, parents clearly preferred atomoxetine. Parents said they were satisfied with the drug's effect overall, as well as with its effect in both morning and evening hours. They were very satisfied with the drug's ability to “allow the child to be himself” during treatment.

Significant increases in blood pressure and heart rate were found for most of the 62 children; 53 experienced an average increase of 2.4 mm Hg in both diastolic and systolic blood pressure. Fifty-seven children experienced an average increase in heart rate of 9 beats per minute. There were no other ECG changes, including in the QT interval.