Key clinical point: The 2-year follow-up results of the phase 3 DISCOVER 2 study revealed the robust and sustained efficacy of 100 mg guselkumab every 4 weeks (Q4W) and 100 mg guselkumab every 8 weeks (Q8W) in improving signs and symptoms of psoriatic arthritis (PsA) in biologic-naive patients along with a consistent safety profile.

Major finding: At week 100, at least 20% improvement in American College of Rheumatology criteria was achieved by 76%, 74%, and 68% of patients who received guselkumab Q4W, guselkumab Q8W, and placebo, respectively, indicating a durable response. No new safety signals were identified.

Study details: Findings are from the phase 3 DISCOVER 2 study including 739 biologic-naive patients with active PsA, who were randomly assigned to 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo. A total of 652 patients completed treatment through week 100.

Disclosures: This study was funded by Janssen Research & Development, LLC, a Johnson & Johnson company. Six authors declared being employees and stockholders of Johnson & Johnson, and the others reported ties with several sources, including Janssen.

Source: McInnes IB et al. Arthritis Rheumatol. 2021(Nov 1). Doi: 10.1002/art.42010.

Key clinical point: The 2-year follow-up results of the phase 3 DISCOVER 2 study revealed the robust and sustained efficacy of 100 mg guselkumab every 4 weeks (Q4W) and 100 mg guselkumab every 8 weeks (Q8W) in improving signs and symptoms of psoriatic arthritis (PsA) in biologic-naive patients along with a consistent safety profile.

Major finding: At week 100, at least 20% improvement in American College of Rheumatology criteria was achieved by 76%, 74%, and 68% of patients who received guselkumab Q4W, guselkumab Q8W, and placebo, respectively, indicating a durable response. No new safety signals were identified.

Study details: Findings are from the phase 3 DISCOVER 2 study including 739 biologic-naive patients with active PsA, who were randomly assigned to 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo. A total of 652 patients completed treatment through week 100.

Disclosures: This study was funded by Janssen Research & Development, LLC, a Johnson & Johnson company. Six authors declared being employees and stockholders of Johnson & Johnson, and the others reported ties with several sources, including Janssen.

Source: McInnes IB et al. Arthritis Rheumatol. 2021(Nov 1). Doi: 10.1002/art.42010.

Key clinical point: The 2-year follow-up results of the phase 3 DISCOVER 2 study revealed the robust and sustained efficacy of 100 mg guselkumab every 4 weeks (Q4W) and 100 mg guselkumab every 8 weeks (Q8W) in improving signs and symptoms of psoriatic arthritis (PsA) in biologic-naive patients along with a consistent safety profile.

Major finding: At week 100, at least 20% improvement in American College of Rheumatology criteria was achieved by 76%, 74%, and 68% of patients who received guselkumab Q4W, guselkumab Q8W, and placebo, respectively, indicating a durable response. No new safety signals were identified.

Study details: Findings are from the phase 3 DISCOVER 2 study including 739 biologic-naive patients with active PsA, who were randomly assigned to 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo. A total of 652 patients completed treatment through week 100.

Disclosures: This study was funded by Janssen Research & Development, LLC, a Johnson & Johnson company. Six authors declared being employees and stockholders of Johnson & Johnson, and the others reported ties with several sources, including Janssen.

Source: McInnes IB et al. Arthritis Rheumatol. 2021(Nov 1). Doi: 10.1002/art.42010.

Key clinical point: Pregnant women with psoriatic arthritis (PsA), particularly those requiring antirheumatic treatment, are at increased risk for adverse pregnancy outcomes.

Major finding: Pregnancy in PsA vs. non-PsA women were associated with increased risk for preterm birth (adjusted odds ratio [aOR] 1.69; 95% CI 1.27-2.24), elective cesarean delivery (CD; aOR 1.77; 95% CI 1.43-2.20), and emergency CD (aOR 1.42; 95% CI 1.10-1.84) with the risk even more pronounced in pregnancies in women with PsA with exposure to antirheumatic treatment any time before or during pregnancy (preterm birth: aOR 1.98; 95% CI 1.27-2.86; elective CD: aOR 1.96; 95% CI 1.47-2.63; and emergency CD: aOR 1.67; 95% CI 1.18-2.36).

Study details: This was a cohort study including 921 pregnancies in patients with PsA matched with 9,210 pregnancies in non-PsA patients.

Disclosures: This study did not receive any funding. None of the authors declared any conflict of interests.

Source: Remaeus K et al. Arthritis Rheumatol. 2021 (Oct 20). Doi: 10.1002/art.41985.

Key clinical point: Pregnant women with psoriatic arthritis (PsA), particularly those requiring antirheumatic treatment, are at increased risk for adverse pregnancy outcomes.

Major finding: Pregnancy in PsA vs. non-PsA women were associated with increased risk for preterm birth (adjusted odds ratio [aOR] 1.69; 95% CI 1.27-2.24), elective cesarean delivery (CD; aOR 1.77; 95% CI 1.43-2.20), and emergency CD (aOR 1.42; 95% CI 1.10-1.84) with the risk even more pronounced in pregnancies in women with PsA with exposure to antirheumatic treatment any time before or during pregnancy (preterm birth: aOR 1.98; 95% CI 1.27-2.86; elective CD: aOR 1.96; 95% CI 1.47-2.63; and emergency CD: aOR 1.67; 95% CI 1.18-2.36).

Study details: This was a cohort study including 921 pregnancies in patients with PsA matched with 9,210 pregnancies in non-PsA patients.

Disclosures: This study did not receive any funding. None of the authors declared any conflict of interests.

Source: Remaeus K et al. Arthritis Rheumatol. 2021 (Oct 20). Doi: 10.1002/art.41985.

Key clinical point: Pregnant women with psoriatic arthritis (PsA), particularly those requiring antirheumatic treatment, are at increased risk for adverse pregnancy outcomes.

Major finding: Pregnancy in PsA vs. non-PsA women were associated with increased risk for preterm birth (adjusted odds ratio [aOR] 1.69; 95% CI 1.27-2.24), elective cesarean delivery (CD; aOR 1.77; 95% CI 1.43-2.20), and emergency CD (aOR 1.42; 95% CI 1.10-1.84) with the risk even more pronounced in pregnancies in women with PsA with exposure to antirheumatic treatment any time before or during pregnancy (preterm birth: aOR 1.98; 95% CI 1.27-2.86; elective CD: aOR 1.96; 95% CI 1.47-2.63; and emergency CD: aOR 1.67; 95% CI 1.18-2.36).

Study details: This was a cohort study including 921 pregnancies in patients with PsA matched with 9,210 pregnancies in non-PsA patients.

Disclosures: This study did not receive any funding. None of the authors declared any conflict of interests.

Source: Remaeus K et al. Arthritis Rheumatol. 2021 (Oct 20). Doi: 10.1002/art.41985.

Key clinical point: In patients with psoriatic arthritis (PsA), joint swelling was more closely related to and better predicted ultrasound-defined inflammation and active synovitis at 1 year than joint tenderness.

Major finding: Swollen joint count correlated better with greyscale and power Doppler (PD) joint scores (correlation coefficient [r] 0.37 and 0.47, respectively) than tender joint count (PD-joint score; r 0.33). Ultrasound verified active synovitis at 12-month follow-up was better predicted by swelling (odds ratio [OR] 6.33; 95% CI 3.70-10.83) vs. tenderness (OR 3.58; 95% CI 2.29-5.58) at baseline.

Study details: Findings are from a prospective study including 83 patients with PsA who underwent clinical and ultrasound examinations at 2 visits scheduled 12 months apart.

Disclosures: This work was funded by Pfizer. The authors declared no conflict of interests.

Source: Bosch P et al. Rheumatology. 2021;keab764 (Oct 21). Doi: 10.1093/rheumatology/keab764.

Key clinical point: In patients with psoriatic arthritis (PsA), joint swelling was more closely related to and better predicted ultrasound-defined inflammation and active synovitis at 1 year than joint tenderness.

Major finding: Swollen joint count correlated better with greyscale and power Doppler (PD) joint scores (correlation coefficient [r] 0.37 and 0.47, respectively) than tender joint count (PD-joint score; r 0.33). Ultrasound verified active synovitis at 12-month follow-up was better predicted by swelling (odds ratio [OR] 6.33; 95% CI 3.70-10.83) vs. tenderness (OR 3.58; 95% CI 2.29-5.58) at baseline.

Study details: Findings are from a prospective study including 83 patients with PsA who underwent clinical and ultrasound examinations at 2 visits scheduled 12 months apart.

Disclosures: This work was funded by Pfizer. The authors declared no conflict of interests.

Source: Bosch P et al. Rheumatology. 2021;keab764 (Oct 21). Doi: 10.1093/rheumatology/keab764.

Key clinical point: In patients with psoriatic arthritis (PsA), joint swelling was more closely related to and better predicted ultrasound-defined inflammation and active synovitis at 1 year than joint tenderness.

Major finding: Swollen joint count correlated better with greyscale and power Doppler (PD) joint scores (correlation coefficient [r] 0.37 and 0.47, respectively) than tender joint count (PD-joint score; r 0.33). Ultrasound verified active synovitis at 12-month follow-up was better predicted by swelling (odds ratio [OR] 6.33; 95% CI 3.70-10.83) vs. tenderness (OR 3.58; 95% CI 2.29-5.58) at baseline.

Study details: Findings are from a prospective study including 83 patients with PsA who underwent clinical and ultrasound examinations at 2 visits scheduled 12 months apart.

Disclosures: This work was funded by Pfizer. The authors declared no conflict of interests.

Source: Bosch P et al. Rheumatology. 2021;keab764 (Oct 21). Doi: 10.1093/rheumatology/keab764.

Key clinical point: The risk for serious infections (SI) was significantly lower in patients with psoriatic arthritis (PsA) vs. patients with rheumatoid arthritis (RA) who were receiving tumor necrosis factor inhibitors (TNFi).

Major finding: The crude incidence rate for SI was lower in patients with PsA (2.16; 95% CI 1.66-2.81) vs. those with RA (4.17; 95% CI 3.52-4.95). Patients with PsA vs. RA still had a lower risk of contracting SI even after adjusting for multiple factors (adjusted hazard ratio 0.65; P = .025).

Study details: Findings are from a prospective observational multicenter study including 1,352 and 1,007 patients with RA and PsA, respectively, from the Norwegian-Disease Modifying Anti-Rheumatic Drug Registry. A total of 3,169 TNFi treatment courses were included in the study.

Disclosures: This study was funded by South-Eastern Health Authority and received partial support from AbbVie, BMS, MSD, Pfizer, Roche, and UCB. The authors report receiving personal fees and grants from the above-mentioned sources and other pharmaceutical companies.

Source: Christensen IE et al. Ann Rheum Dis. 2021 (Oct 8). Doi: 10.1136/annrheumdis-2021-221007.

Key clinical point: The risk for serious infections (SI) was significantly lower in patients with psoriatic arthritis (PsA) vs. patients with rheumatoid arthritis (RA) who were receiving tumor necrosis factor inhibitors (TNFi).

Major finding: The crude incidence rate for SI was lower in patients with PsA (2.16; 95% CI 1.66-2.81) vs. those with RA (4.17; 95% CI 3.52-4.95). Patients with PsA vs. RA still had a lower risk of contracting SI even after adjusting for multiple factors (adjusted hazard ratio 0.65; P = .025).

Study details: Findings are from a prospective observational multicenter study including 1,352 and 1,007 patients with RA and PsA, respectively, from the Norwegian-Disease Modifying Anti-Rheumatic Drug Registry. A total of 3,169 TNFi treatment courses were included in the study.

Disclosures: This study was funded by South-Eastern Health Authority and received partial support from AbbVie, BMS, MSD, Pfizer, Roche, and UCB. The authors report receiving personal fees and grants from the above-mentioned sources and other pharmaceutical companies.

Source: Christensen IE et al. Ann Rheum Dis. 2021 (Oct 8). Doi: 10.1136/annrheumdis-2021-221007.

Key clinical point: The risk for serious infections (SI) was significantly lower in patients with psoriatic arthritis (PsA) vs. patients with rheumatoid arthritis (RA) who were receiving tumor necrosis factor inhibitors (TNFi).

Major finding: The crude incidence rate for SI was lower in patients with PsA (2.16; 95% CI 1.66-2.81) vs. those with RA (4.17; 95% CI 3.52-4.95). Patients with PsA vs. RA still had a lower risk of contracting SI even after adjusting for multiple factors (adjusted hazard ratio 0.65; P = .025).

Study details: Findings are from a prospective observational multicenter study including 1,352 and 1,007 patients with RA and PsA, respectively, from the Norwegian-Disease Modifying Anti-Rheumatic Drug Registry. A total of 3,169 TNFi treatment courses were included in the study.

Disclosures: This study was funded by South-Eastern Health Authority and received partial support from AbbVie, BMS, MSD, Pfizer, Roche, and UCB. The authors report receiving personal fees and grants from the above-mentioned sources and other pharmaceutical companies.

Source: Christensen IE et al. Ann Rheum Dis. 2021 (Oct 8). Doi: 10.1136/annrheumdis-2021-221007.

Key clinical point: Upadacitinib continued to demonstrate improvement in clinical manifestations of psoriatic arthritis (PsA) through week 56 in patients with inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs) with no new adverse events.

Major finding: Consistent with week 24, a higher proportion of patients achieved at least 20% improvement in the American College of Rheumatology criteria with upadacitinib (15 mg, 74.4%; 30 mg, 74.7%) vs. adalimumab (68.5%; P = .046) at week 56. No new safety signals were identified.

Study details: Findings are from an analysis of 1,419 patients with active PsA and inadequate response to at least 1 non-bDMARD who completed 56 weeks of treatment in the phase 3 SELECT-PsA 1 study.

Disclosures: This study was sponsored by AbbVie. The authors reported receiving research grants, honoraria, and consulting fees from or serving as an advisory board member, being an employee, or being shareholders in various companies, including AbbVie.

Source: McInnes IB et al. RMD Open. 2021;7:e001838 (Oct 18). Doi:  10.1136/rmdopen-2021-001838.

Key clinical point: Upadacitinib continued to demonstrate improvement in clinical manifestations of psoriatic arthritis (PsA) through week 56 in patients with inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs) with no new adverse events.

Major finding: Consistent with week 24, a higher proportion of patients achieved at least 20% improvement in the American College of Rheumatology criteria with upadacitinib (15 mg, 74.4%; 30 mg, 74.7%) vs. adalimumab (68.5%; P = .046) at week 56. No new safety signals were identified.

Study details: Findings are from an analysis of 1,419 patients with active PsA and inadequate response to at least 1 non-bDMARD who completed 56 weeks of treatment in the phase 3 SELECT-PsA 1 study.

Disclosures: This study was sponsored by AbbVie. The authors reported receiving research grants, honoraria, and consulting fees from or serving as an advisory board member, being an employee, or being shareholders in various companies, including AbbVie.

Source: McInnes IB et al. RMD Open. 2021;7:e001838 (Oct 18). Doi:  10.1136/rmdopen-2021-001838.

Key clinical point: Upadacitinib continued to demonstrate improvement in clinical manifestations of psoriatic arthritis (PsA) through week 56 in patients with inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs) with no new adverse events.

Major finding: Consistent with week 24, a higher proportion of patients achieved at least 20% improvement in the American College of Rheumatology criteria with upadacitinib (15 mg, 74.4%; 30 mg, 74.7%) vs. adalimumab (68.5%; P = .046) at week 56. No new safety signals were identified.

Study details: Findings are from an analysis of 1,419 patients with active PsA and inadequate response to at least 1 non-bDMARD who completed 56 weeks of treatment in the phase 3 SELECT-PsA 1 study.

Disclosures: This study was sponsored by AbbVie. The authors reported receiving research grants, honoraria, and consulting fees from or serving as an advisory board member, being an employee, or being shareholders in various companies, including AbbVie.

Source: McInnes IB et al. RMD Open. 2021;7:e001838 (Oct 18). Doi:  10.1136/rmdopen-2021-001838.

The newly detected Omicron COVID-19 variant may be highly infectious and less responsive to available vaccines than other variants, but it is too early to know how it compares to the Delta variant, top infectious disease official Anthony S. Fauci, MD, said Nov. 30.

Dr. Fauci, speaking at a White House COVID-19 briefing, said there’s a “very unusual constellation of changes” across the COVID-19 genome that indicates it is unlike any variant we have seen so far.

“This mutational profile is very different from other variants of interest and concern, and although some mutations are also found in Delta, this is not Delta,” Dr. Fauci said. “These mutations have been associated with increased transmissibility and immune evasion.”

Omicron is the fifth designated COVID-19 variant of concern.

Detected first in South Africa, Omicron has been found in 20 countries so far. There are no known cases yet in the United States, but it has been detected in Canada.

Omicron has more than 30 mutations to the spike protein, the part of the virus that binds to human cells, Dr. Fauci said.

Cross-protection from boosters

Though the mutations suggest there is increased transmission of this variant, he said it is too soon to know how this compares to the Delta variant. And although the vaccines may not be as effective against Omicron, Dr. Fauci said there will likely be some protection.

“Remember, as with other variants, although partial immune escape may occur, vaccines, particularly boosters, give a level of antibodies that even with variants like Delta give you a degree of cross-protection, particularly against severe disease,” he said.

“When we say that although these mutations suggest a diminution of protection and a degree of immune evasion, we still, from experience with Delta, can make a reasonable conclusion that you would not eliminate all protection against this particular variant,” Dr. Fauci said.

So far, there is no reason to believe Omicron will cause more severe illness than other variants of concern.

“Although some preliminary information from South Africa suggests no unusual symptoms associated with variant, we do not know, and it is too early to tell,” Dr. Fauci said.

He recommended that people continue to wear masks, wash hands, and avoid crowded indoor venues. Most importantly, he recommended that everyone get their vaccines and boosters.

“One thing has become clear over the last 20 months: We can’t predict the future, but we can be prepared for it,” CDC Director Rochelle P. Walensky, MD, said at the briefing. “We have far more tools to fight the variant today than we did at this time last year.”


A version of this story first appeared on Medscape.com.

The newly detected Omicron COVID-19 variant may be highly infectious and less responsive to available vaccines than other variants, but it is too early to know how it compares to the Delta variant, top infectious disease official Anthony S. Fauci, MD, said Nov. 30.

Dr. Fauci, speaking at a White House COVID-19 briefing, said there’s a “very unusual constellation of changes” across the COVID-19 genome that indicates it is unlike any variant we have seen so far.

“This mutational profile is very different from other variants of interest and concern, and although some mutations are also found in Delta, this is not Delta,” Dr. Fauci said. “These mutations have been associated with increased transmissibility and immune evasion.”

Omicron is the fifth designated COVID-19 variant of concern.

Detected first in South Africa, Omicron has been found in 20 countries so far. There are no known cases yet in the United States, but it has been detected in Canada.

Omicron has more than 30 mutations to the spike protein, the part of the virus that binds to human cells, Dr. Fauci said.

Cross-protection from boosters

Though the mutations suggest there is increased transmission of this variant, he said it is too soon to know how this compares to the Delta variant. And although the vaccines may not be as effective against Omicron, Dr. Fauci said there will likely be some protection.

“Remember, as with other variants, although partial immune escape may occur, vaccines, particularly boosters, give a level of antibodies that even with variants like Delta give you a degree of cross-protection, particularly against severe disease,” he said.

“When we say that although these mutations suggest a diminution of protection and a degree of immune evasion, we still, from experience with Delta, can make a reasonable conclusion that you would not eliminate all protection against this particular variant,” Dr. Fauci said.

So far, there is no reason to believe Omicron will cause more severe illness than other variants of concern.

“Although some preliminary information from South Africa suggests no unusual symptoms associated with variant, we do not know, and it is too early to tell,” Dr. Fauci said.

He recommended that people continue to wear masks, wash hands, and avoid crowded indoor venues. Most importantly, he recommended that everyone get their vaccines and boosters.

“One thing has become clear over the last 20 months: We can’t predict the future, but we can be prepared for it,” CDC Director Rochelle P. Walensky, MD, said at the briefing. “We have far more tools to fight the variant today than we did at this time last year.”


A version of this story first appeared on Medscape.com.

The newly detected Omicron COVID-19 variant may be highly infectious and less responsive to available vaccines than other variants, but it is too early to know how it compares to the Delta variant, top infectious disease official Anthony S. Fauci, MD, said Nov. 30.

Dr. Fauci, speaking at a White House COVID-19 briefing, said there’s a “very unusual constellation of changes” across the COVID-19 genome that indicates it is unlike any variant we have seen so far.

“This mutational profile is very different from other variants of interest and concern, and although some mutations are also found in Delta, this is not Delta,” Dr. Fauci said. “These mutations have been associated with increased transmissibility and immune evasion.”

Omicron is the fifth designated COVID-19 variant of concern.

Detected first in South Africa, Omicron has been found in 20 countries so far. There are no known cases yet in the United States, but it has been detected in Canada.

Omicron has more than 30 mutations to the spike protein, the part of the virus that binds to human cells, Dr. Fauci said.

Cross-protection from boosters

Though the mutations suggest there is increased transmission of this variant, he said it is too soon to know how this compares to the Delta variant. And although the vaccines may not be as effective against Omicron, Dr. Fauci said there will likely be some protection.

“Remember, as with other variants, although partial immune escape may occur, vaccines, particularly boosters, give a level of antibodies that even with variants like Delta give you a degree of cross-protection, particularly against severe disease,” he said.

“When we say that although these mutations suggest a diminution of protection and a degree of immune evasion, we still, from experience with Delta, can make a reasonable conclusion that you would not eliminate all protection against this particular variant,” Dr. Fauci said.

So far, there is no reason to believe Omicron will cause more severe illness than other variants of concern.

“Although some preliminary information from South Africa suggests no unusual symptoms associated with variant, we do not know, and it is too early to tell,” Dr. Fauci said.

He recommended that people continue to wear masks, wash hands, and avoid crowded indoor venues. Most importantly, he recommended that everyone get their vaccines and boosters.

“One thing has become clear over the last 20 months: We can’t predict the future, but we can be prepared for it,” CDC Director Rochelle P. Walensky, MD, said at the briefing. “We have far more tools to fight the variant today than we did at this time last year.”


A version of this story first appeared on Medscape.com.

An antiviral pill from Merck may help some high-risk patients survive a COVID-19 infection or help them stay out of the hospital, even though the risks of taking the drug aren’t yet fully known, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.

The FDA is not bound by the committee’s vote but typically follows its advice.

If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.

The United Kingdom has already authorized the use of Merck’s drug.

“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.

Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.

“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.

Others didn’t agree that the drug should be allowed onto the market.

“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.

Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.

But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.

In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.

On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.

The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.

“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.

“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.

Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.

There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.

Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.

Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.

Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.

Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.

The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.

But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.

Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.

So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.

Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.

“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.

“So we don’t,” Dr. Kartsonis said.

He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.

“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.

Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.

“It was an easy vote for me,” he said.

A version of this article first appeared on Medscape.com.

An antiviral pill from Merck may help some high-risk patients survive a COVID-19 infection or help them stay out of the hospital, even though the risks of taking the drug aren’t yet fully known, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.

The FDA is not bound by the committee’s vote but typically follows its advice.

If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.

The United Kingdom has already authorized the use of Merck’s drug.

“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.

Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.

“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.

Others didn’t agree that the drug should be allowed onto the market.

“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.

Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.

But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.

In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.

On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.

The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.

“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.

“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.

Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.

There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.

Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.

Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.

Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.

Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.

The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.

But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.

Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.

So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.

Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.

“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.

“So we don’t,” Dr. Kartsonis said.

He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.

“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.

Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.

“It was an easy vote for me,” he said.

A version of this article first appeared on Medscape.com.

An antiviral pill from Merck may help some high-risk patients survive a COVID-19 infection or help them stay out of the hospital, even though the risks of taking the drug aren’t yet fully known, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.

The FDA is not bound by the committee’s vote but typically follows its advice.

If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.

The United Kingdom has already authorized the use of Merck’s drug.

“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.

Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.

“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.

Others didn’t agree that the drug should be allowed onto the market.

“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.

Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.

But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.

In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.

On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.

The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.

“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.

“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.

Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.

There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.

Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.

Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.

Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.

Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.

The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.

But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.

Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.

So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.

Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.

“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.

“So we don’t,” Dr. Kartsonis said.

He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.

“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.

Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.

“It was an easy vote for me,” he said.

A version of this article first appeared on Medscape.com.

Correct answer: A. Intravenous proton pump inhibitor drip. 
 
Rationale  
It is important to understand the initial management of patients with bleeding esophageal varices. With voluminous hematemesis, especially from a proximal source like the esophagus, airway protection is crucial so this patient should be intubated. Patients like this are at high risk to develop infected ascites so IV antibiotics should be given. Antibiotics have been shown to decrease mortality in cirrhotic patients admitted with GI bleeding. Somatostatin analogs decrease portal inflow by causing splanchnic vasoconstriction and have been proven to achieve hemostasis and decrease the risk of rebleeding. One has to be cautious with resuscitation efforts, as excessive resuscitation can lead to accelerated bleeding due to increased portal pressures. However, this patient's Hemoglobin concentration is well below the threshold that warrants transfusion, so giving him PRBCs is appropriate. In the acute setting of an upper GI bleed, proton pump inhibitors work to help optimize platelet function by increasing gastric pH. Since the source here is varices in the more pH neutral esophageal environment, intravenous PPI likely has little effect in the acute setting. However after band ligation is performed, it may help decrease the risk of forming post-banding ulcers. Since this patient's banding was performed a month ago, this episode of bleeding is more likely to be from recurrent varices than from a post-banding ulcer.  
 
References  
Garcia-Tsao G et al. Hepatology. 2007 Sep;46(3):922-38.  
Tripathi D et al. Gut. 2015 Nov;64(11):1680-704.

Correct answer: A. Intravenous proton pump inhibitor drip. 
 
Rationale  
It is important to understand the initial management of patients with bleeding esophageal varices. With voluminous hematemesis, especially from a proximal source like the esophagus, airway protection is crucial so this patient should be intubated. Patients like this are at high risk to develop infected ascites so IV antibiotics should be given. Antibiotics have been shown to decrease mortality in cirrhotic patients admitted with GI bleeding. Somatostatin analogs decrease portal inflow by causing splanchnic vasoconstriction and have been proven to achieve hemostasis and decrease the risk of rebleeding. One has to be cautious with resuscitation efforts, as excessive resuscitation can lead to accelerated bleeding due to increased portal pressures. However, this patient's Hemoglobin concentration is well below the threshold that warrants transfusion, so giving him PRBCs is appropriate. In the acute setting of an upper GI bleed, proton pump inhibitors work to help optimize platelet function by increasing gastric pH. Since the source here is varices in the more pH neutral esophageal environment, intravenous PPI likely has little effect in the acute setting. However after band ligation is performed, it may help decrease the risk of forming post-banding ulcers. Since this patient's banding was performed a month ago, this episode of bleeding is more likely to be from recurrent varices than from a post-banding ulcer.  
 
References  
Garcia-Tsao G et al. Hepatology. 2007 Sep;46(3):922-38.  
Tripathi D et al. Gut. 2015 Nov;64(11):1680-704.

Correct answer: A. Intravenous proton pump inhibitor drip. 
 
Rationale  
It is important to understand the initial management of patients with bleeding esophageal varices. With voluminous hematemesis, especially from a proximal source like the esophagus, airway protection is crucial so this patient should be intubated. Patients like this are at high risk to develop infected ascites so IV antibiotics should be given. Antibiotics have been shown to decrease mortality in cirrhotic patients admitted with GI bleeding. Somatostatin analogs decrease portal inflow by causing splanchnic vasoconstriction and have been proven to achieve hemostasis and decrease the risk of rebleeding. One has to be cautious with resuscitation efforts, as excessive resuscitation can lead to accelerated bleeding due to increased portal pressures. However, this patient's Hemoglobin concentration is well below the threshold that warrants transfusion, so giving him PRBCs is appropriate. In the acute setting of an upper GI bleed, proton pump inhibitors work to help optimize platelet function by increasing gastric pH. Since the source here is varices in the more pH neutral esophageal environment, intravenous PPI likely has little effect in the acute setting. However after band ligation is performed, it may help decrease the risk of forming post-banding ulcers. Since this patient's banding was performed a month ago, this episode of bleeding is more likely to be from recurrent varices than from a post-banding ulcer.  
 
References  
Garcia-Tsao G et al. Hepatology. 2007 Sep;46(3):922-38.  
Tripathi D et al. Gut. 2015 Nov;64(11):1680-704.

Correct answer: A. Diphyllobothrium latum. 
 
Rationale  
This is likely a tapeworm infection with Diphyllobothrium latum. D. latum infection can be acquired from ingesting certain forms of freshwater fish, and those who consume raw fish, including sushi, are at increased risk. The classical manifestation of infection with D. latum is megaloblastic anemia due to vitamin B12 deficiency. D. latum has a unique affinity for vitamin B12 and therefore competes with the host for absorption. Humans become infected with Taenia by ingesting raw or undercooked infected meat containing cysticerci. Infection with Hymenolepis is common in children secondary to breaches in fecal-oral hygiene. Most infections are asymptomatic.  
 
Reference  
Webb C, Cabada MM. Curr Opin Infect Dis. 2017 Oct;30(5):504-10. 

Correct answer: A. Diphyllobothrium latum. 
 
Rationale  
This is likely a tapeworm infection with Diphyllobothrium latum. D. latum infection can be acquired from ingesting certain forms of freshwater fish, and those who consume raw fish, including sushi, are at increased risk. The classical manifestation of infection with D. latum is megaloblastic anemia due to vitamin B12 deficiency. D. latum has a unique affinity for vitamin B12 and therefore competes with the host for absorption. Humans become infected with Taenia by ingesting raw or undercooked infected meat containing cysticerci. Infection with Hymenolepis is common in children secondary to breaches in fecal-oral hygiene. Most infections are asymptomatic.  
 
Reference  
Webb C, Cabada MM. Curr Opin Infect Dis. 2017 Oct;30(5):504-10. 

Correct answer: A. Diphyllobothrium latum. 
 
Rationale  
This is likely a tapeworm infection with Diphyllobothrium latum. D. latum infection can be acquired from ingesting certain forms of freshwater fish, and those who consume raw fish, including sushi, are at increased risk. The classical manifestation of infection with D. latum is megaloblastic anemia due to vitamin B12 deficiency. D. latum has a unique affinity for vitamin B12 and therefore competes with the host for absorption. Humans become infected with Taenia by ingesting raw or undercooked infected meat containing cysticerci. Infection with Hymenolepis is common in children secondary to breaches in fecal-oral hygiene. Most infections are asymptomatic.  
 
Reference  
Webb C, Cabada MM. Curr Opin Infect Dis. 2017 Oct;30(5):504-10. 

FIRST OF 2 PARTS

A thorough evaluation can identify modifiable factors and guide treatment

Sleep problems are common among children and adolescents,¹ with prevalence rates of 25% to 40%.^2-4 Young children most commonly exhibit what is referred to as bedtime problems and night wakenings, whereas children in middle childhood (age 4 to 12) through adolescence (age 13 to 17) report insomnia. For many children, these problems persist.³ Insufficient sleep in children and adolescents worsens inattention, daytime fatigue, and cognitive and behavioral deficits.⁵ Assessment and treatment of sleep problems in children and adolescents is critical because poor sleep among youth increases the risk for depression, self-harm, and suicide,^6,7 increases family stress, and decreases parental well-being.¹

This 2-part article describes the assessment, diagnosis, and treatment of sleep problems among children and adolescents. In part 1, we focus on:

• sleep architecture (circadian rhythms, stages of sleep)
• sleep in healthy youth (age 6 to 17) and those with attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and anxiety
• how to assess sleep, and the differential diagnosis of behavioral sleep problems in pediatric patients.

In Part 2, we will cover psychotherapeutic and psychopharmacologic interventions for youth with insomnia, and describe an effective approach to consultation with pediatric sleep medicine specialists.

How much sleep do children and adolescents need?

Throughout their development, children spend 40% to 50% of their time asleep. Sleep schedules are based on circadian rhythms, which are physical, mental, and behavioral changes that follow an approximately 24-hour cycle. Human circadian rhythm varies between 24 and 25 hours and is vital in determining our sleep patterns. Exposure to sunlight drives our circadian rhythm, sending signals to our bodies to “turn on” melatonin production at night (ie, 9 pm melatonin secretion starts) and “turn off” melatonin secretion in the morning (ie, 7:30 am) in adults. Exposure to sunlight also drives circadian rhythms for children, and melatonin secretion production occurs earlier in the evening for children. Families are encouraged to expose children to bright light in the morning by taking an early walk, eating breakfast in a sunny room, or having adolescents open up the window shades rather than keeping their eyes shielded from the sun.² How sleepy or alert a child could be is determined by the duration and quality of a child’s previous sleep, and how long they have been awake (“sleep drive”).² The 3 states of sleep architecture are wake; non-rapid eye movement sleep; and rapid eye movement sleep (“dreaming” sleep) (Box²).

Box

Sleep needs also change predictably throughout the lifespan. The National Sleep Foundation guidelines for sleep duration provide clinicians and parents with a range of recommended sleep for each stage of development. Infants require 14 to 17 hours of sleep, whereas adolescents need 8 to 10 hours by age 14 to 17.⁸ The key for clinicians is to determine if the child is within the recommended range, and how they are functioning on the number of hours of sleep they report. This allows for variation in how much sleep an individual child might need while acknowledging that some children within a specific age group might need more or less sleep than other children of the same age.

Sleep in healthy youth: Middle childhood

School-age children (age 6 to 12) typically need 9 to 10 hours of sleep over a 24-hour period.² This developmental period is especially important for children to develop healthy sleep habits; however, developmentally appropriate cognitive and social/emotional factors might interfere with the quality and quantity of sleep. Middle childhood is a time when children can understand the dangers of the outside world (ie, violence, health problems) and resulting anxiety can disrupt sleep. Parents usually are less involved in bedtime as children approach adolescence, which leads to later bedtimes. At this stage, many children begin to take on more serious roles in their academics and extracurricular activities, peer relationships become more important, and use of electronics (eg, television, video games, internet, and handheld devices) increases—all of which compete with sleep.⁹ Frequent sleep issues during middle childhood include:

• irregular sleep-wake schedules
• later bedtimes
• decreased nighttime sleep
• increased caffeine intake
• reduced parental presence at bedtime
• daytime sleepiness.³

In school-age children, regular napping, falling asleep during short car rides, and daytime fatigue at school or home are cause for concern. When these symptoms are present, an evaluation is warranted.

Sleep in healthy youth: Adolescence

The National Sleep Foundation recommends adolescents obtain 8 to 10 hours of sleep per night; for some adolescents, as much as 11 hours of sleep per night might be appropriate.⁸ However, this contrasts with findings from the National Sleep Foundation’s Sleep in America Poll, which revealed that 75% of 12th graders report <8 hours of sleep nightly.¹⁰ Many adolescents experience delayed sleep phase syndrome or delayed sleep-wake phase disorder, which involves a persistent phase shift of >2 hours in the sleep-wake schedule that conflicts with the adolescent’s school, work, or lifestyle demands.¹¹ Such circadian rhythm disorders typically result from a poor match between the sleep-wake schedule and the demands of the adolescent’s life, or a failure to synchronize their internal clock with a 24-hour circadian clock.¹² Children typically become tired after sunset, but puberty is associated with reduced slow-wave sleep and changes in circadian rhythms. As a result, a 3-hour delay (delayed phase preference) is common among adolescents. At approximately age 20, people start to become tired after sunset and awaken earlier in the morning—a pattern driven by sunlight and the timing of melatonin release that will remain stable until the sixth decade of life.

Continue to: Effects of chronic sleep deprivation...

Most older studies of sleep loss examined the impact of total sleep loss (sleep deprivation) rather than the effect of partial sleep loss or sleep restriction, a more commonly experienced phenomenon. More recent research shows that a cumulative sleep deficit could cause the body to override voluntary wakefulness and a sleep-deprived individual can experience brief “microsleeps” where they are unaware and lose attention/wakefulness for several seconds.² This can be deadly if a sleep-deprived adolescent experiences microsleeps while driving.¹³

There is a well-studied correlation between chronic sleep deprivation and increased body mass index in children.¹⁴ This might be caused by reduction in physical activity as well as alterations in the “hunger hormones”—ghrelin and leptin—that have been observed with sleep deprivation.^15-17 Other studies have noted decreased glucose tolerance, reduced insulin sensitivity, and catecholamine and cortisol secretion abnormalities, which place children at higher risk for metabolic syndrome and hypertension.^13,18 Sleep deprivation also is associated with mood and anxiety disorders and is an independent risk factor for substance use and suicidal ideation among adolescents.¹⁹ Sleep deprivation increases impairments in impulse control, concentration, and attention, which could be especially problematic in school-age children.

How sleep is assessed

The sleep history is the first step in evaluating a child or adolescent for a sleep disorder. The sleep history includes exploring the chief complaint, sleep patterns and schedules, bedtime routines, and nocturnal and daytime behaviors (Table).

Chief complaint

Behavioral sleep specialists will assess the primary problem with everyone involved in the child’s bedtime.²⁰ This might include parents (custodial and noncustodial), grandparents, or stepparents as well as the child/adolescent. This important step can reveal a sleep disorder or an inappropriately early bedtime relative to the child’s development. During this assessment, ask detailed questions about how long the sleep problem has persisted, the frequency of sleep problems, and any precipitating stressors. Parents and caregivers can review strategies they have tried, and for how long and to what extent interventions were implemented consistently to result in change.

Sleep patterns and schedules

Review the child/adolescent’s typical sleep patterns and behaviors. Ask parents and caregivers, as well as the patient, about general sleep schedules for the past few weeks or a typical 2-week time period.² A behavioral assessment of sleep should include asking families about how the child/adolescent sleeps during the week and over the weekend, and if school-year sleep differs from summer or holiday sleep schedules. These questions can illuminate how long a sleep problem has been occurring and what sleep habits might be contributing to the problem. Bedtime

Determine if there is a set bedtime or if the child goes to bed when they wish. It is important to ascertain if the bedtime is age-appropriate, if weekday and weekend bedtimes differ, and to what extent extracurricular activities or school demands impact bedtime. Assess the consistency of the bedtime, the nature of bedtime routines (eg, is the child engaging in stimulating activities before bed), where the bedtime routine occurs (eg, sibling’s room, parents’ room, child’s room), and what role (if any) electronic devices play.²

Nocturnal behaviors

Assessment should include a series of questions and age-specific questionnaires to focus on what behaviors occur at night, including awakenings. Parents should be asked how frequent night awakenings occur, how long arousals last, and how the child signals for the parent (eg, calling out, climbing into parents’ bed).² Additionally, ask how parents respond and what is required to help the child fall back asleep (eg, rocking, soothing, feeding). The presence of nightmares, night terrors, parasomnias, and sleep-related breathing disorders also must be assessed.²⁰

Daytime behaviors

A sleep history should include assessment of daytime functioning, including daytime sleepiness, fatigue, morning waking, and functioning during school, extracurriculars, and homework. For children and teens, falling asleep in the car, while in school, or during passive activities (meals, conversation) suggests insufficient sleep, sleep disruption, or excessive daytime sleepiness.²

Continue to: Sleep disruption in youth with psychiatric disorders...

Sleep disruption in youth with psychiatric disorders

Disordered sleep is common across psychiatric disorders. The National Comorbidity Survey Adolescent Supplement—a nationally representative cross-sectional survey of adolescents (N = 10,123)—found that a later weeknight bedtime, shorter weeknight sleep duration, and greater weekend bedtime delay increased the risk of developing a mood, anxiety, or substance use (including nicotine) disorder, and suicidality. These risk factors also were associated with lower “perceived mental and physical health.”²¹ Clinicians should routinely obtain a sleep history in children and adolescents with these disorders. Consider using the sleep screening tool BEARS:

• Bedtime issues
• Excessive daytime sleepiness
• Awakenings
• Regularity and duration of sleep
• Snoring.

ADHD

Up to one-half of children and adolescents with ADHD experience sleep problems,^22,23 including delayed sleep onset, bedtime resistance, daytime fatigue, and feeling groggy in the morning beyond what is typical (>20 minutes). Pharmacotherapy for ADHD contributes to sleep disturbances^24,25 while sleep deprivation exacerbates inattention and hyperactivity. In youth with ADHD, restless leg syndrome, periodic limb movement disorder, and sleep-disordered breathing disorder are more common than in the general population.

Depressive disorders

Up to three-quarters of depressed children and 90% of depressed adolescents report sleep disturbances, including initial, middle, and terminal insomnia as well as hypersomnia.²⁶ Disrupted sleep in pediatric patients with major depressive disorder could be moderated by the patient’s age, with depressive symptoms more common among adolescents (age 12 to 17) than among younger children (age 6 to 11).²⁷ Successful treatment of depression fails to relieve dyssomnia in 10% of children. Sleep problems that persist after successfully treating a depressive episode could increase the risk of another depressive episode.²⁸

Anxiety disorders

Sleep problems are common among children and adolescents with anxiety disorders.²⁹ Longitudinal data from >900 children found that symptoms of sleep disturbance in early childhood were correlated with experiencing an anxiety disorder 20 years later.³⁰ Fears related to the dark or monsters under the bed that are developmentally appropriate for younger children may interfere with sleep. However, in anxious children, fears might also be related to separation, sleeping alone, worry about the loss of a loved one, concerns about personal safety, fear of frightening dreams, or concerns about academics and social relationships. Anxious individuals ruminate about their worries, and this might be especially true for children at bedtime, when there are limited distractions from ruminative fears.³¹ Bedtime resistance, parental involvement in bedtime rituals, and cultural factors related to sleep also could play a role for children with anxiety symptoms and sleep problems.

Having an anxiety disorder is significantly associated with an increased risk of insomnia; however, 73% of the time anxiety symptoms precede an insomnia diagnosis.²⁹ Sleep problems and anxiety symptoms might have a reciprocal influence on one another; tiredness that results from sleep problems could exacerbate anxiety, which further worsens sleep problems.

A large body of research on sleep and anxiety reveals that abuse or exposure to trauma significantly affects sleep.³¹ Common sleep problems for children with posttraumatic stress disorder include difficulty falling asleep, maintaining sleep, and parasomnias of bedwetting and nightmares.^31,32 Compared with depressed and non-abused children, those with history of abuse have prolonged sleep latency, decreased sleep efficiency, and higher levels of activity during the night.³³ In addition to the relationship between anxiety disorders and sleep disorders, many of the selective serotonin reuptake inhibitors—which are the first-line pharmacotherapy for pediatric anxiety disorders^34,35—could affect sleep in anxious youth.³⁶

A bridge to treatment

A thorough assessment can help identify modifiable factors and guide treatment selections. In Part 2 of this article, we will describe healthy sleep practices, cognitive-behavioral therapy for insomnia, when pharmacotherapy might be indicated, and the evidence supporting several medications commonly used to treat pediatric insomnia. We also will discuss factors to consider when seeking consultation with a pediatric behavioral sleep specialist.

FIRST OF 2 PARTS

A thorough evaluation can identify modifiable factors and guide treatment

Sleep problems are common among children and adolescents,¹ with prevalence rates of 25% to 40%.^2-4 Young children most commonly exhibit what is referred to as bedtime problems and night wakenings, whereas children in middle childhood (age 4 to 12) through adolescence (age 13 to 17) report insomnia. For many children, these problems persist.³ Insufficient sleep in children and adolescents worsens inattention, daytime fatigue, and cognitive and behavioral deficits.⁵ Assessment and treatment of sleep problems in children and adolescents is critical because poor sleep among youth increases the risk for depression, self-harm, and suicide,^6,7 increases family stress, and decreases parental well-being.¹

This 2-part article describes the assessment, diagnosis, and treatment of sleep problems among children and adolescents. In part 1, we focus on:

• sleep architecture (circadian rhythms, stages of sleep)
• sleep in healthy youth (age 6 to 17) and those with attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and anxiety
• how to assess sleep, and the differential diagnosis of behavioral sleep problems in pediatric patients.

In Part 2, we will cover psychotherapeutic and psychopharmacologic interventions for youth with insomnia, and describe an effective approach to consultation with pediatric sleep medicine specialists.

How much sleep do children and adolescents need?

Throughout their development, children spend 40% to 50% of their time asleep. Sleep schedules are based on circadian rhythms, which are physical, mental, and behavioral changes that follow an approximately 24-hour cycle. Human circadian rhythm varies between 24 and 25 hours and is vital in determining our sleep patterns. Exposure to sunlight drives our circadian rhythm, sending signals to our bodies to “turn on” melatonin production at night (ie, 9 pm melatonin secretion starts) and “turn off” melatonin secretion in the morning (ie, 7:30 am) in adults. Exposure to sunlight also drives circadian rhythms for children, and melatonin secretion production occurs earlier in the evening for children. Families are encouraged to expose children to bright light in the morning by taking an early walk, eating breakfast in a sunny room, or having adolescents open up the window shades rather than keeping their eyes shielded from the sun.² How sleepy or alert a child could be is determined by the duration and quality of a child’s previous sleep, and how long they have been awake (“sleep drive”).² The 3 states of sleep architecture are wake; non-rapid eye movement sleep; and rapid eye movement sleep (“dreaming” sleep) (Box²).

Box

Sleep needs also change predictably throughout the lifespan. The National Sleep Foundation guidelines for sleep duration provide clinicians and parents with a range of recommended sleep for each stage of development. Infants require 14 to 17 hours of sleep, whereas adolescents need 8 to 10 hours by age 14 to 17.⁸ The key for clinicians is to determine if the child is within the recommended range, and how they are functioning on the number of hours of sleep they report. This allows for variation in how much sleep an individual child might need while acknowledging that some children within a specific age group might need more or less sleep than other children of the same age.

Sleep in healthy youth: Middle childhood

School-age children (age 6 to 12) typically need 9 to 10 hours of sleep over a 24-hour period.² This developmental period is especially important for children to develop healthy sleep habits; however, developmentally appropriate cognitive and social/emotional factors might interfere with the quality and quantity of sleep. Middle childhood is a time when children can understand the dangers of the outside world (ie, violence, health problems) and resulting anxiety can disrupt sleep. Parents usually are less involved in bedtime as children approach adolescence, which leads to later bedtimes. At this stage, many children begin to take on more serious roles in their academics and extracurricular activities, peer relationships become more important, and use of electronics (eg, television, video games, internet, and handheld devices) increases—all of which compete with sleep.⁹ Frequent sleep issues during middle childhood include:

• irregular sleep-wake schedules
• later bedtimes
• decreased nighttime sleep
• increased caffeine intake
• reduced parental presence at bedtime
• daytime sleepiness.³

In school-age children, regular napping, falling asleep during short car rides, and daytime fatigue at school or home are cause for concern. When these symptoms are present, an evaluation is warranted.

Sleep in healthy youth: Adolescence

The National Sleep Foundation recommends adolescents obtain 8 to 10 hours of sleep per night; for some adolescents, as much as 11 hours of sleep per night might be appropriate.⁸ However, this contrasts with findings from the National Sleep Foundation’s Sleep in America Poll, which revealed that 75% of 12th graders report <8 hours of sleep nightly.¹⁰ Many adolescents experience delayed sleep phase syndrome or delayed sleep-wake phase disorder, which involves a persistent phase shift of >2 hours in the sleep-wake schedule that conflicts with the adolescent’s school, work, or lifestyle demands.¹¹ Such circadian rhythm disorders typically result from a poor match between the sleep-wake schedule and the demands of the adolescent’s life, or a failure to synchronize their internal clock with a 24-hour circadian clock.¹² Children typically become tired after sunset, but puberty is associated with reduced slow-wave sleep and changes in circadian rhythms. As a result, a 3-hour delay (delayed phase preference) is common among adolescents. At approximately age 20, people start to become tired after sunset and awaken earlier in the morning—a pattern driven by sunlight and the timing of melatonin release that will remain stable until the sixth decade of life.

Continue to: Effects of chronic sleep deprivation...

Most older studies of sleep loss examined the impact of total sleep loss (sleep deprivation) rather than the effect of partial sleep loss or sleep restriction, a more commonly experienced phenomenon. More recent research shows that a cumulative sleep deficit could cause the body to override voluntary wakefulness and a sleep-deprived individual can experience brief “microsleeps” where they are unaware and lose attention/wakefulness for several seconds.² This can be deadly if a sleep-deprived adolescent experiences microsleeps while driving.¹³

There is a well-studied correlation between chronic sleep deprivation and increased body mass index in children.¹⁴ This might be caused by reduction in physical activity as well as alterations in the “hunger hormones”—ghrelin and leptin—that have been observed with sleep deprivation.^15-17 Other studies have noted decreased glucose tolerance, reduced insulin sensitivity, and catecholamine and cortisol secretion abnormalities, which place children at higher risk for metabolic syndrome and hypertension.^13,18 Sleep deprivation also is associated with mood and anxiety disorders and is an independent risk factor for substance use and suicidal ideation among adolescents.¹⁹ Sleep deprivation increases impairments in impulse control, concentration, and attention, which could be especially problematic in school-age children.

How sleep is assessed

The sleep history is the first step in evaluating a child or adolescent for a sleep disorder. The sleep history includes exploring the chief complaint, sleep patterns and schedules, bedtime routines, and nocturnal and daytime behaviors (Table).

Chief complaint

Behavioral sleep specialists will assess the primary problem with everyone involved in the child’s bedtime.²⁰ This might include parents (custodial and noncustodial), grandparents, or stepparents as well as the child/adolescent. This important step can reveal a sleep disorder or an inappropriately early bedtime relative to the child’s development. During this assessment, ask detailed questions about how long the sleep problem has persisted, the frequency of sleep problems, and any precipitating stressors. Parents and caregivers can review strategies they have tried, and for how long and to what extent interventions were implemented consistently to result in change.

Sleep patterns and schedules

Review the child/adolescent’s typical sleep patterns and behaviors. Ask parents and caregivers, as well as the patient, about general sleep schedules for the past few weeks or a typical 2-week time period.² A behavioral assessment of sleep should include asking families about how the child/adolescent sleeps during the week and over the weekend, and if school-year sleep differs from summer or holiday sleep schedules. These questions can illuminate how long a sleep problem has been occurring and what sleep habits might be contributing to the problem. Bedtime

Determine if there is a set bedtime or if the child goes to bed when they wish. It is important to ascertain if the bedtime is age-appropriate, if weekday and weekend bedtimes differ, and to what extent extracurricular activities or school demands impact bedtime. Assess the consistency of the bedtime, the nature of bedtime routines (eg, is the child engaging in stimulating activities before bed), where the bedtime routine occurs (eg, sibling’s room, parents’ room, child’s room), and what role (if any) electronic devices play.²

Nocturnal behaviors

Assessment should include a series of questions and age-specific questionnaires to focus on what behaviors occur at night, including awakenings. Parents should be asked how frequent night awakenings occur, how long arousals last, and how the child signals for the parent (eg, calling out, climbing into parents’ bed).² Additionally, ask how parents respond and what is required to help the child fall back asleep (eg, rocking, soothing, feeding). The presence of nightmares, night terrors, parasomnias, and sleep-related breathing disorders also must be assessed.²⁰

Daytime behaviors

A sleep history should include assessment of daytime functioning, including daytime sleepiness, fatigue, morning waking, and functioning during school, extracurriculars, and homework. For children and teens, falling asleep in the car, while in school, or during passive activities (meals, conversation) suggests insufficient sleep, sleep disruption, or excessive daytime sleepiness.²

Continue to: Sleep disruption in youth with psychiatric disorders...

Sleep disruption in youth with psychiatric disorders

Disordered sleep is common across psychiatric disorders. The National Comorbidity Survey Adolescent Supplement—a nationally representative cross-sectional survey of adolescents (N = 10,123)—found that a later weeknight bedtime, shorter weeknight sleep duration, and greater weekend bedtime delay increased the risk of developing a mood, anxiety, or substance use (including nicotine) disorder, and suicidality. These risk factors also were associated with lower “perceived mental and physical health.”²¹ Clinicians should routinely obtain a sleep history in children and adolescents with these disorders. Consider using the sleep screening tool BEARS:

• Bedtime issues
• Excessive daytime sleepiness
• Awakenings
• Regularity and duration of sleep
• Snoring.

ADHD

Up to one-half of children and adolescents with ADHD experience sleep problems,^22,23 including delayed sleep onset, bedtime resistance, daytime fatigue, and feeling groggy in the morning beyond what is typical (>20 minutes). Pharmacotherapy for ADHD contributes to sleep disturbances^24,25 while sleep deprivation exacerbates inattention and hyperactivity. In youth with ADHD, restless leg syndrome, periodic limb movement disorder, and sleep-disordered breathing disorder are more common than in the general population.

Depressive disorders

Up to three-quarters of depressed children and 90% of depressed adolescents report sleep disturbances, including initial, middle, and terminal insomnia as well as hypersomnia.²⁶ Disrupted sleep in pediatric patients with major depressive disorder could be moderated by the patient’s age, with depressive symptoms more common among adolescents (age 12 to 17) than among younger children (age 6 to 11).²⁷ Successful treatment of depression fails to relieve dyssomnia in 10% of children. Sleep problems that persist after successfully treating a depressive episode could increase the risk of another depressive episode.²⁸

Anxiety disorders

Sleep problems are common among children and adolescents with anxiety disorders.²⁹ Longitudinal data from >900 children found that symptoms of sleep disturbance in early childhood were correlated with experiencing an anxiety disorder 20 years later.³⁰ Fears related to the dark or monsters under the bed that are developmentally appropriate for younger children may interfere with sleep. However, in anxious children, fears might also be related to separation, sleeping alone, worry about the loss of a loved one, concerns about personal safety, fear of frightening dreams, or concerns about academics and social relationships. Anxious individuals ruminate about their worries, and this might be especially true for children at bedtime, when there are limited distractions from ruminative fears.³¹ Bedtime resistance, parental involvement in bedtime rituals, and cultural factors related to sleep also could play a role for children with anxiety symptoms and sleep problems.

Having an anxiety disorder is significantly associated with an increased risk of insomnia; however, 73% of the time anxiety symptoms precede an insomnia diagnosis.²⁹ Sleep problems and anxiety symptoms might have a reciprocal influence on one another; tiredness that results from sleep problems could exacerbate anxiety, which further worsens sleep problems.

A large body of research on sleep and anxiety reveals that abuse or exposure to trauma significantly affects sleep.³¹ Common sleep problems for children with posttraumatic stress disorder include difficulty falling asleep, maintaining sleep, and parasomnias of bedwetting and nightmares.^31,32 Compared with depressed and non-abused children, those with history of abuse have prolonged sleep latency, decreased sleep efficiency, and higher levels of activity during the night.³³ In addition to the relationship between anxiety disorders and sleep disorders, many of the selective serotonin reuptake inhibitors—which are the first-line pharmacotherapy for pediatric anxiety disorders^34,35—could affect sleep in anxious youth.³⁶

A bridge to treatment

A thorough assessment can help identify modifiable factors and guide treatment selections. In Part 2 of this article, we will describe healthy sleep practices, cognitive-behavioral therapy for insomnia, when pharmacotherapy might be indicated, and the evidence supporting several medications commonly used to treat pediatric insomnia. We also will discuss factors to consider when seeking consultation with a pediatric behavioral sleep specialist.

FIRST OF 2 PARTS

A thorough evaluation can identify modifiable factors and guide treatment

Sleep problems are common among children and adolescents,¹ with prevalence rates of 25% to 40%.^2-4 Young children most commonly exhibit what is referred to as bedtime problems and night wakenings, whereas children in middle childhood (age 4 to 12) through adolescence (age 13 to 17) report insomnia. For many children, these problems persist.³ Insufficient sleep in children and adolescents worsens inattention, daytime fatigue, and cognitive and behavioral deficits.⁵ Assessment and treatment of sleep problems in children and adolescents is critical because poor sleep among youth increases the risk for depression, self-harm, and suicide,^6,7 increases family stress, and decreases parental well-being.¹

This 2-part article describes the assessment, diagnosis, and treatment of sleep problems among children and adolescents. In part 1, we focus on:

• sleep architecture (circadian rhythms, stages of sleep)
• sleep in healthy youth (age 6 to 17) and those with attention-deficit/hyperactivity disorder (ADHD), depressive disorders, and anxiety
• how to assess sleep, and the differential diagnosis of behavioral sleep problems in pediatric patients.

In Part 2, we will cover psychotherapeutic and psychopharmacologic interventions for youth with insomnia, and describe an effective approach to consultation with pediatric sleep medicine specialists.

How much sleep do children and adolescents need?

Throughout their development, children spend 40% to 50% of their time asleep. Sleep schedules are based on circadian rhythms, which are physical, mental, and behavioral changes that follow an approximately 24-hour cycle. Human circadian rhythm varies between 24 and 25 hours and is vital in determining our sleep patterns. Exposure to sunlight drives our circadian rhythm, sending signals to our bodies to “turn on” melatonin production at night (ie, 9 pm melatonin secretion starts) and “turn off” melatonin secretion in the morning (ie, 7:30 am) in adults. Exposure to sunlight also drives circadian rhythms for children, and melatonin secretion production occurs earlier in the evening for children. Families are encouraged to expose children to bright light in the morning by taking an early walk, eating breakfast in a sunny room, or having adolescents open up the window shades rather than keeping their eyes shielded from the sun.² How sleepy or alert a child could be is determined by the duration and quality of a child’s previous sleep, and how long they have been awake (“sleep drive”).² The 3 states of sleep architecture are wake; non-rapid eye movement sleep; and rapid eye movement sleep (“dreaming” sleep) (Box²).

Box

Sleep needs also change predictably throughout the lifespan. The National Sleep Foundation guidelines for sleep duration provide clinicians and parents with a range of recommended sleep for each stage of development. Infants require 14 to 17 hours of sleep, whereas adolescents need 8 to 10 hours by age 14 to 17.⁸ The key for clinicians is to determine if the child is within the recommended range, and how they are functioning on the number of hours of sleep they report. This allows for variation in how much sleep an individual child might need while acknowledging that some children within a specific age group might need more or less sleep than other children of the same age.

Sleep in healthy youth: Middle childhood

School-age children (age 6 to 12) typically need 9 to 10 hours of sleep over a 24-hour period.² This developmental period is especially important for children to develop healthy sleep habits; however, developmentally appropriate cognitive and social/emotional factors might interfere with the quality and quantity of sleep. Middle childhood is a time when children can understand the dangers of the outside world (ie, violence, health problems) and resulting anxiety can disrupt sleep. Parents usually are less involved in bedtime as children approach adolescence, which leads to later bedtimes. At this stage, many children begin to take on more serious roles in their academics and extracurricular activities, peer relationships become more important, and use of electronics (eg, television, video games, internet, and handheld devices) increases—all of which compete with sleep.⁹ Frequent sleep issues during middle childhood include:

• irregular sleep-wake schedules
• later bedtimes
• decreased nighttime sleep
• increased caffeine intake
• reduced parental presence at bedtime
• daytime sleepiness.³

In school-age children, regular napping, falling asleep during short car rides, and daytime fatigue at school or home are cause for concern. When these symptoms are present, an evaluation is warranted.

Sleep in healthy youth: Adolescence

The National Sleep Foundation recommends adolescents obtain 8 to 10 hours of sleep per night; for some adolescents, as much as 11 hours of sleep per night might be appropriate.⁸ However, this contrasts with findings from the National Sleep Foundation’s Sleep in America Poll, which revealed that 75% of 12th graders report <8 hours of sleep nightly.¹⁰ Many adolescents experience delayed sleep phase syndrome or delayed sleep-wake phase disorder, which involves a persistent phase shift of >2 hours in the sleep-wake schedule that conflicts with the adolescent’s school, work, or lifestyle demands.¹¹ Such circadian rhythm disorders typically result from a poor match between the sleep-wake schedule and the demands of the adolescent’s life, or a failure to synchronize their internal clock with a 24-hour circadian clock.¹² Children typically become tired after sunset, but puberty is associated with reduced slow-wave sleep and changes in circadian rhythms. As a result, a 3-hour delay (delayed phase preference) is common among adolescents. At approximately age 20, people start to become tired after sunset and awaken earlier in the morning—a pattern driven by sunlight and the timing of melatonin release that will remain stable until the sixth decade of life.

Continue to: Effects of chronic sleep deprivation...

Most older studies of sleep loss examined the impact of total sleep loss (sleep deprivation) rather than the effect of partial sleep loss or sleep restriction, a more commonly experienced phenomenon. More recent research shows that a cumulative sleep deficit could cause the body to override voluntary wakefulness and a sleep-deprived individual can experience brief “microsleeps” where they are unaware and lose attention/wakefulness for several seconds.² This can be deadly if a sleep-deprived adolescent experiences microsleeps while driving.¹³

There is a well-studied correlation between chronic sleep deprivation and increased body mass index in children.¹⁴ This might be caused by reduction in physical activity as well as alterations in the “hunger hormones”—ghrelin and leptin—that have been observed with sleep deprivation.^15-17 Other studies have noted decreased glucose tolerance, reduced insulin sensitivity, and catecholamine and cortisol secretion abnormalities, which place children at higher risk for metabolic syndrome and hypertension.^13,18 Sleep deprivation also is associated with mood and anxiety disorders and is an independent risk factor for substance use and suicidal ideation among adolescents.¹⁹ Sleep deprivation increases impairments in impulse control, concentration, and attention, which could be especially problematic in school-age children.

How sleep is assessed

The sleep history is the first step in evaluating a child or adolescent for a sleep disorder. The sleep history includes exploring the chief complaint, sleep patterns and schedules, bedtime routines, and nocturnal and daytime behaviors (Table).

Chief complaint

Behavioral sleep specialists will assess the primary problem with everyone involved in the child’s bedtime.²⁰ This might include parents (custodial and noncustodial), grandparents, or stepparents as well as the child/adolescent. This important step can reveal a sleep disorder or an inappropriately early bedtime relative to the child’s development. During this assessment, ask detailed questions about how long the sleep problem has persisted, the frequency of sleep problems, and any precipitating stressors. Parents and caregivers can review strategies they have tried, and for how long and to what extent interventions were implemented consistently to result in change.

Sleep patterns and schedules

Review the child/adolescent’s typical sleep patterns and behaviors. Ask parents and caregivers, as well as the patient, about general sleep schedules for the past few weeks or a typical 2-week time period.² A behavioral assessment of sleep should include asking families about how the child/adolescent sleeps during the week and over the weekend, and if school-year sleep differs from summer or holiday sleep schedules. These questions can illuminate how long a sleep problem has been occurring and what sleep habits might be contributing to the problem. Bedtime

Determine if there is a set bedtime or if the child goes to bed when they wish. It is important to ascertain if the bedtime is age-appropriate, if weekday and weekend bedtimes differ, and to what extent extracurricular activities or school demands impact bedtime. Assess the consistency of the bedtime, the nature of bedtime routines (eg, is the child engaging in stimulating activities before bed), where the bedtime routine occurs (eg, sibling’s room, parents’ room, child’s room), and what role (if any) electronic devices play.²

Nocturnal behaviors

Assessment should include a series of questions and age-specific questionnaires to focus on what behaviors occur at night, including awakenings. Parents should be asked how frequent night awakenings occur, how long arousals last, and how the child signals for the parent (eg, calling out, climbing into parents’ bed).² Additionally, ask how parents respond and what is required to help the child fall back asleep (eg, rocking, soothing, feeding). The presence of nightmares, night terrors, parasomnias, and sleep-related breathing disorders also must be assessed.²⁰

Daytime behaviors

A sleep history should include assessment of daytime functioning, including daytime sleepiness, fatigue, morning waking, and functioning during school, extracurriculars, and homework. For children and teens, falling asleep in the car, while in school, or during passive activities (meals, conversation) suggests insufficient sleep, sleep disruption, or excessive daytime sleepiness.²

Continue to: Sleep disruption in youth with psychiatric disorders...

Sleep disruption in youth with psychiatric disorders

Disordered sleep is common across psychiatric disorders. The National Comorbidity Survey Adolescent Supplement—a nationally representative cross-sectional survey of adolescents (N = 10,123)—found that a later weeknight bedtime, shorter weeknight sleep duration, and greater weekend bedtime delay increased the risk of developing a mood, anxiety, or substance use (including nicotine) disorder, and suicidality. These risk factors also were associated with lower “perceived mental and physical health.”²¹ Clinicians should routinely obtain a sleep history in children and adolescents with these disorders. Consider using the sleep screening tool BEARS:

• Bedtime issues
• Excessive daytime sleepiness
• Awakenings
• Regularity and duration of sleep
• Snoring.

ADHD

Up to one-half of children and adolescents with ADHD experience sleep problems,^22,23 including delayed sleep onset, bedtime resistance, daytime fatigue, and feeling groggy in the morning beyond what is typical (>20 minutes). Pharmacotherapy for ADHD contributes to sleep disturbances^24,25 while sleep deprivation exacerbates inattention and hyperactivity. In youth with ADHD, restless leg syndrome, periodic limb movement disorder, and sleep-disordered breathing disorder are more common than in the general population.

Depressive disorders

Up to three-quarters of depressed children and 90% of depressed adolescents report sleep disturbances, including initial, middle, and terminal insomnia as well as hypersomnia.²⁶ Disrupted sleep in pediatric patients with major depressive disorder could be moderated by the patient’s age, with depressive symptoms more common among adolescents (age 12 to 17) than among younger children (age 6 to 11).²⁷ Successful treatment of depression fails to relieve dyssomnia in 10% of children. Sleep problems that persist after successfully treating a depressive episode could increase the risk of another depressive episode.²⁸

Anxiety disorders

Sleep problems are common among children and adolescents with anxiety disorders.²⁹ Longitudinal data from >900 children found that symptoms of sleep disturbance in early childhood were correlated with experiencing an anxiety disorder 20 years later.³⁰ Fears related to the dark or monsters under the bed that are developmentally appropriate for younger children may interfere with sleep. However, in anxious children, fears might also be related to separation, sleeping alone, worry about the loss of a loved one, concerns about personal safety, fear of frightening dreams, or concerns about academics and social relationships. Anxious individuals ruminate about their worries, and this might be especially true for children at bedtime, when there are limited distractions from ruminative fears.³¹ Bedtime resistance, parental involvement in bedtime rituals, and cultural factors related to sleep also could play a role for children with anxiety symptoms and sleep problems.

Having an anxiety disorder is significantly associated with an increased risk of insomnia; however, 73% of the time anxiety symptoms precede an insomnia diagnosis.²⁹ Sleep problems and anxiety symptoms might have a reciprocal influence on one another; tiredness that results from sleep problems could exacerbate anxiety, which further worsens sleep problems.

A large body of research on sleep and anxiety reveals that abuse or exposure to trauma significantly affects sleep.³¹ Common sleep problems for children with posttraumatic stress disorder include difficulty falling asleep, maintaining sleep, and parasomnias of bedwetting and nightmares.^31,32 Compared with depressed and non-abused children, those with history of abuse have prolonged sleep latency, decreased sleep efficiency, and higher levels of activity during the night.³³ In addition to the relationship between anxiety disorders and sleep disorders, many of the selective serotonin reuptake inhibitors—which are the first-line pharmacotherapy for pediatric anxiety disorders^34,35—could affect sleep in anxious youth.³⁶

A bridge to treatment

A thorough assessment can help identify modifiable factors and guide treatment selections. In Part 2 of this article, we will describe healthy sleep practices, cognitive-behavioral therapy for insomnia, when pharmacotherapy might be indicated, and the evidence supporting several medications commonly used to treat pediatric insomnia. We also will discuss factors to consider when seeking consultation with a pediatric behavioral sleep specialist.