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SPECIAL ARTICLE

Pharmacologic Management of Insomnia in Children
and Adolescents: Consensus Statement
Jodi A. Mindell, PhDa, Graham Emslie, MDb, Jeffrey Blumer, MD, PhDc, Myron Genel, MDd, Daniel Glaze, MDe, Anna Ivanenko, MD, PhDf,
Kyle Johnson, MDg, Carol Rosen, MDc, Frank Steinberg, DOh, Thomas Roth, PhDi, Bridget Banasj
a

Department of Psychology, Saint Joseph’s University and Sleep Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; bDepartment of Psychiatry,
University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; cDepartment of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland,
Ohio; dChild Health Research Center, Department of Pediatrics, School of Medicine, Yale University, New Haven, Connecticut; eDepartments of Pediatrics and Neurology,
Baylor College of Medicine, Houston, Texas; fDepartments of Psychiatry and Neurosciences, Loyola University Medical Center, Chicago, Illinois; gDepartments of
Psychiatry and Pediatrics, Oregon Health and Science University, Portland, Oregon; hMedical Consultant, Evanston, Illinois; iSleep Disorders and Research Center, Henry
Ford Hospital, Detroit, Michigan; jMedical Writer, Boston, Massachusetts
Financial Disclosure: Dr Mindell is a member of the speaker’s bureau of King and Sepracor and a consultant for Pfizer, Johnson’s Baby, and Wyeth. Dr Emslie is a member of the speaker’s bureau of McNeil and a
consultant for Eli Lilly, GlaxoSmithKline, Forest, Pfizer, and Wyeth-Ayerst. Drs Blumer, Glaze, and Steinberg are consultants for Sanofi-Aventis. Dr Johnson is a member of the speaker’s bureau of Sanofi-Aventis.
Dr Rosen is a consultant for Sanofi-Aventis and Cephalon. Dr Roth is a member of the speaker’s bureau of Sanofi-Aventis and is a consultant for Acadia, Actelion, AstraZeneca, Aventis, Cephalon, Cypress, Eli
Lilly, GlaxoSmithKline, Hypnion, King, Lundbeck, McNeil, Merck, Neurocrine, Neurogen, NovaDel, Organon, Orginer, Pfizer, Roche, Sanofi, Sepracor, Somaxon, Syrex, Takeda, Transoral, Vanda, Vivometrics, and
Wyeth. Dr Genel is a consultant for Pfizer and Off the Record Research.

ABSTRACT
OBJECTIVE. The purpose of this work was to develop a consensus statement on the
current status and future role for pharmacologic management of insomnia in
children and adolescents.

www.pediatrics.org/cgi/doi/10.1542/
peds.2005-1693

METHOD. The National Sleep Foundation, in collaboration with Best Practice Project

doi:10.1542/peds.2005-1693

Management, Inc, convened expert representatives involved in the study and
treatment of pediatric insomnia and conducted a 2-day conference to examine the
role of pharmacologic management of pediatric insomnia and to make recommendations regarding the development of clinical trials in this area. After a series of
presentations providing background on the current knowledge of pediatric insomnia and its treatment alternatives, workgroups provided recommendations for the
evaluation of pharmacologic treatment of insomnia in specific populations of
children and adolescents and developed guidelines for the core methodologic
issues relevant to the design of clinical trials. The group developed consensus
recommendations for clinical trials in this area encompassing: (1) high-priority
patient populations for research, (2) inclusion/exclusion criteria, (3) outcome
measures, (4) ethical considerations unique to clinical trials involving children and
adolescents, and (5) priorities for future research that will enhance the understanding of pediatric insomnia.

This work was presented in part at the
Pharmacological Management of Insomnia
in Children and Adolescents conference;
November 1–2, 2004; Baltimore, MD

RESULTS. Conference participants unanimously agreed that there is a need for phar-

PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright © 2006 by the
American Academy of Pediatrics

macologic management of pediatric insomnia. Furthermore, the widespread use of
“hypnotic” and psychotropic medications for children in the absence of safety and
efficacy data indicates a knowledge gap about the best pharmacologic practices for

Key Words
insomnia, clinical trials, pediatric,
pharmacotherapy, sleep disorders
Abbreviations
ADHD—attention-deficit/hyperactivity
disorder
PDD—pervasive developmental disorder
MDD—major depressive disorder
DSPS— delayed sleep phase syndrome
PSG—polysomnography
Accepted for publication Jan 23, 2006
Address correspondence to Jodi A. Mindell,
PhD, Department of Psychology, Saint
Joseph’s University, Philadelphia, PA 19131.
E-mail: jmindell@sju.edu

PEDIATRICS Volume 117, Number 6, June 2006

e1223

The specific objectives of the conference were to (1) develop a consensus definition of pediatric insomnia.9–11 Compounding the situation is the absence of pharmaceuticals currently indicated for hypnotic use in the pediatric population.6–8 New studies continue to demonstrate the negative consequences of sleeplessness in children and adolescents. staff of the Food and Drug Administration and National Institutes of Health. the National Sleep Foundation.” It was agreed that priority should be given to insomnia studies in children with attention-deficit/hyperactivity disorder and those with pervasive developmental disorders/autism spectrum disorder. BACKGROUND T HERE IS A great need to understand and effectively treat pediatric insomnia. including antihistamines. current research on behavioral and pharmacologic therapy for treating pediatric insomnia. thera- . Thus. antidepressants. Conference Responding to the above concerns. further research is needed regarding the most appropriate treatment regimes for both the general pediatric population and subpopulations in terms of commonly prescribed medications to treat both their primary disorder and comorbid insomnia. leading parents to administer overthe-counter treatments and physicians to prescribe drugs without a proven record of safety and effectiveness in children or a determination of pediatric dosing. and (3) to suggest areas of further research that could enhance the understanding of pediatric insomnia. The lack of appropriately labeled drugs is counter. and (3) develop recommendations for clinical trials in the pharmacologic management of pediatric insomnia. including hyperactivity. Families of children with sleep disturbances also suffer. Participants included clinical researchers with experience in childhood and adult insomnia. convened a 2-day conference on the “Pharmacological Management of Insomnia in Children and Adolescents” in November 2004. The treatment of pediatric insomnia is an unmet medical need. There was also agreement on the need for pharmacokinetic and pharmacodynamic studies to determine appropriate dose levels and to evaluate safety with a wide range of doses. exhibiting negative effects on daytime function and well-being. in collaboration with Best Practice Project Management. to determine in what subpopulations that need was the greatest. The goals of this meeting were to (1) determine whether there was a medical need for the treatment of insomnia in children and. The first part of the conference consisted of plenary presentations to establish a common background. poor concentration. suicide risk. background on populations of children with increased rates of insomnia where the need for treatment is the greatest. pharmaceutical industry representatives. (2) understand the current status and need for nonpharmacologic and pharmacologic management of pediatric insomnia. if so. These included discussions concerning an appropriate definition of pediatric insomnia. severity. however. and members of the National Sleep Foundation. (2) to develop recommendations for clinical trials that would pave the way for pediatric use of insomnia medications. simply prescribing a reduced dosage of a drug approved for adult usage or using drugs indicated for other conditions is not a satisfactory solution. pediatric insomnia in children and adolescents is a widespread problem. including clonidine. as well as elevated levels of family stress. children with attention-deficit/hyperactivity disorder (ADHD) or depression were commonly prescribed treatments for insomnia. and antihistamines. In addition. Although extensive population-based studies have yet to be conducted. Before appropriate pharmacologic management guidelines can be developed. rigorous. consolidation. Children often demonstrate safety profiles that differ significantly from adults. as well as pediatric-specific clinical research considerations. frequency. the prevalence of pediatric insomnia in children that goes beyond bedtime refusal and night wakings ranges from 1% to 6% in the general population and is as high as 50 –75% in children with neurodevelopmental or psychiatric comorbidities. Despite the widespread use of prescription therapies and other products. CONCLUSIONS. to current use. large-scale clinical trials of pediatric insomnia treatment are vitally needed to provide information to the clinician on the safety and efficacy of prescription and over-thecounter agents for the management of pediatric insomnia. mood stabilizers. including dose definition.12–18 A recent survey of community-based pediatricians indicated that a majority of responders had recommended either OTC sleep aids (75%) and/or prescription medication (50%) for the management of e1224 MINDELL et al pediatric insomnia.19 In addition. irritability. impulsiveness. duration. Attendees reached consensus on methodologic issues in the study of pharmacologic treatment of pediatric insomnia including agreeing on a definition of pediatric insomnia as “repeated difficulty with sleep initiation. many medications that are commonly used as hypnotics in children are being used for their sedative adverse effects rather than for primary effects on sleep/wake mechanisms or hyperarousal.1–5 Although case definitions (in terms of age. restlessness. and duration of symptoms) and sample populations (healthy versus children with neurologic or psychiatric comorbidities) have varied. As a result. Inc. little data exist on their efficacy for the treatment of insomnia in children and adolescents. or quality that occurs despite age-appropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family.management of pediatric insomnia. and poor memory.

” “functional. and chronic neurologic disorders.peutic end points. with higher prevalence in children with other neurodevelopmental or psychiatric comorbidities. duration. Pediatric insomnia also differs from the adult manifestation in that children. as a result of sleep loss. this article presents a summary of the consensus recommendations reached by the group. there are several difficulties inherent in working with this population. is a less understood condition. Second. Rett’s disorder. The workgroups presented their work-in-process to the entire group twice. or quality that occurs despite age-appropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family. Participants were assigned to workgroups. and limit setting regarding such practices as late night television viewing) and proven behavioral strategies (such as extinction programs or bedtime fading) should be the first lines of treatment. including behavioral. Two primary pediatric populations at high risk for insomnia were identified: (1) children with neuropsychiatric disorders. (3) the PDD patient’s general lack of responsiveness to behavior therapy. childhood disintegrative disorder. necessitating the incorporation of a diverse population. The clinical experience of the participants and results of studies conducted in recent years indicate that these patients have low response rates to behavioral therapy in the management of their sleep disturbances. Although children with PDD would experience a real benefit from hypnotics. they will likely remain PEDIATRICS Volume 117. including pervasive developmental disorders ([PDDs] autistic disorder. Good sleep practices (avoiding caffeinated beverages.25–29 PDD patients were recommended because of (1) the significant number of children with PDD. such as Angelman syndrome. medical. Participants in the conference were primarily concerned with children who do not respond to behavioral interventions and who would be candidates for pharmacologic management of their insomnia and. Number 6.22–24 This insomnia can be the end result of multiple etiologies. if PDD patients are treated with psychotropic medications. and each workgroup was charged with developing consensus recommendations for the development of guidelines for clinical trials for the pharmacologic management of pediatric insomnia. June 2006 e1225 . Unlike insomnia in the adult population. First. thus. genetic disorders. often exhibit paradoxical behaviors. All of the participants agreed to the proposed recommendations as described below. Definition of Pediatric Insomnia Insomnia in adults is a generally well-understood condition that is highly prevalent. providing the opportunity for all conference participants to hear and comment on the efforts of other groups. and regulatory and ethical issues. and (4) the chronic nature of their insomnia. Children with PDD (incorporates autism spectrum disorder) were identified as one of the highest priority populations of children with neuropsychiatric disorders for future trials of pharmacologic sleep agents. The phrases “age-appropriate. (2) the well-established diagnostic criterion for the various disorders included in the PDD category. This group of children is composed of many subpopulations with varying degrees of impairment and symptomatology. age appropriate sleep/wake schedules. Pediatric Insomnia Repeated difficulty with sleep initiation. Study Design for Clinical Trials in Pediatric Insomnia Participants Neuropsychiatric Disorders With Comorbid Insomnia Children with neuropsychiatric disorders commonly exhibit chronic sleep disturbances. psychiatric. pediatric insomnia is often reported by a caregiver and is usually described as difficulty in falling asleep and/or staying asleep. and (2) children with a variety of other medical conditions and sleep disorders associated with insomnia symptoms. This definition intentionally includes both children with behavioral insomnia and those with insomnia that persists despite proper sleep hygiene. with ⬃10% of the general adult population experiencing chronic insomnia. The definition endorsed by the group is a version of the International Classification of Sleep Disorders-2 definition for adult insomnia that has been modified to take into account the uniqueness of insomnia in the pediatric population. Asperger’s disorder. consolidation. The remainder of the conference consisted of working sessions for the development of consensus recommendations. including hyperactivity and restlessness. however. ADHD. thus. a suitable definition of pediatric insomnia was an important focus of this consensus meeting. and psychosocial. a diagnosis of PDD encompasses a wide range of impairment levels and comorbidities. and PDD not otherwise specified). such as epilepsy and Tourette’s disorder.” and “for the child and/or family” were added to the International Classification of Sleep Disorders-2 definition of insomnia for the pediatric population.20–21 Insomnia in children. an important group to target for clinical trials. Prevalence estimates are 1– 6% (10 –30% if including bedtime refusal and night wakings). This patient population commonly has disruptive nighttime behaviors and difficulties with sleep onset and maintenance that interfere with adequate sleep time. making this population relatively easy to define and recruit for study. which negatively impact daytime functioning. In light of these nuances. environmental. and that the reporter of the symptoms is often a parent or other caregiver.

as a result.53 was rejected for initial studies . separation anxiety disorder. children in this group are very likely to be prescribed other short-term medications (eg. studies could potentially provide generalizable insights into other pediatric insomnias. with the insomnia often resolving without treatment. because insomnia is frequently associated with depression. opiates) for the management of the acute problem. may lead to recruiting challenges because of its purported low prevalence rate and lack of descriptive clinical detail and definition in pediatric populations. research into this area is needed. or the loss of someone close to the child was also eliminated. Thus. Furthermore. It is believed. However. Behavioral insomnia of childhood (sleep onset association type. the PDD group of children deserved study and that as long as an individual had been stable on a treatment regimen for a reasonable period of time. an area of medical need. and cancer and its treatments.46. there is evidence from several small studies that improved sleep in children with ADHD can lead to a reduction of ADHD symptoms. a disorder in which there e1226 MINDELL et al seems to be fairly consistent reports of sleep disturbance. another potential area of future study is MDD. Whether this improvement is directly related to the effect of the medication or is a result of overall improvement in the depression remains unclear. or travel). chronic pain. this group was chosen for study because of (1) the prevalence of the condition. Studies have indicated that as many as 75% of children with MDD have sleep problems. Finally. Children with ADHD frequently have comorbid disorders and are often taking medication that may confound data interpretation. that. such as asthma. that these patients may not be the best choice for early clinical trials. behavioral insomnia of childhood.and lifestyle-related sleep phase delays that are especially common during adolescence. short-term insomnia (commonly because of acute pain. including major depressive disorder (MDD). The other noted medical disorders associated with insomnia may also not be ideal populations for early clinical trials. such as cystic fibrosis and chronic pain related to rheumatological disorders. generalized anxiety disorder. and. In both adults and children.40–45 Insomnia associated with DSPS has a significant impact on daytime functioning. Medical Disorders With Comorbid Insomnia and/or Primary Sleep Disorders Several medical and primary sleep disorders for which pharmacologic management for sleep disturbances may be appropriate were identified. and (3) considerable evidence from multiple studies suggesting that ADHD patients experience higher rates of sleep disturbances than the general pediatric population. psychophysiological (primary) insomnia.47 Pharmacologic treatment may be an important adjunct to circadian treatments for this sleep disorder. and posttraumatic stress disorder.37 Thus. Although insomnia is common in children with chronic medical conditions. there is at least initial evidence that hypnotics may play an important role in improving sleep in children with depression. those with DSPS may have lower occurrences of comorbidities and may be less likely to be on medication. limit setting type. however. overall. There is significant concern. potentially making them an interesting population for studies of insomnia pharmacotherapy. Acute insomnia that might be associated with a hospitalization. they should be eligible for study participation. because the condition is too transient. including delayed sleep phase syndrome (DSPS). Although there are few pediatric studies on the impact of antidepressants on sleep in children. Finally. however. children with ADHD as a group are the most likely to be receiving off-label hypnotic therapy. a fracture. drug interactions may complicate the assessment of a hypnotic agent. rheumatic disorders. there is moderate concern that some patients in this population may be unwilling or unable to tolerate the procedures necessary for sleep monitoring. cancer. because there is often confusion between DSPS and biological.49 Two common forms of primary insomnia in adults. In addition. Children with ADHD were identified as another highpriority group of children with neuropsychiatric disorders for study.on them and. that children with stable ADHD who also had a stable medication dosage and/or behavioral treatments are an important therapeutic target. insomnia is a frequent symptom of mood and anxiety disorders. In addition. As with children with PDD. It was recommended. Unlike children with ADHD and PDD. bipolar disorder. hospitalization. however. Furthermore.30–36 Studies have indicated that as many as 50 – 60% of children with ADHD experience sleep problems. and insomnia associated with medical conditions. there have been no polysomnographic studies of anxiety disorder-associated insomnia other than in children with posttraumatic stress disorder.48. (2) the existence of standard diagnostic criteria for identification and evaluation of ADHD. a few reports have suggested that sleep improves with some antidepressant treatments. psychophysiologic and idiopathic insomnia. No treatment studies have been reported. hence. The role of hypnotics in anxiety disorders is less clear than for ADHD and depression.50–52 the lack of data about the prevalence of insomnia symptoms and the heterogenous sources of insomnia would make these clinical populations less desirable for initial study. The final area of potential study suggested within the neuropsychiatric disorders was that of insomnia associated with anxiety disorders in children. and combined type) was rejected because of the established efficacy of behavioral therapy.38. cystic fibrosis. issues involved in studying this population were also discussed. however.39 To date.

such as sleep apnea. Number 6.” In addition. children should only be included if there is no temporal relationship between the onset of the insomnia and the use of the specific medication. were also recommended exclusions unless they are the primary study group. such as hand-held computer-based diaries and interactive voice reporting services. and the heterogeneity of the conditions. conference participants agreed that children should not be excluded from clinical studies if they are on additional pharmacologic therapies for their primary disorder. using disease-specific validation criteria to ensure that the study population is adequately homogeneous. respiratory movements. may not tolerate the multiple physiologic sensors placed during the PSG procedure. the most common measure. comorbid psychiatric disorders. especially those with PDD. Although actigraphy is a reliable measure of total sleep time. had the potential to be harmful. Three months was suggested as an appropriate length of time to demonstrate “stability. Actigraphy. Outcome Measures Polysomnography and Actigraphy Polysomnography (PSG) is considered the “gold standard” for studying sleep. For some children. Individuals passing the first screen should then be evaluated for insomnia using age-appropriate criteria for bedtimes. cannot be used to screen for an underlying sleep disorder. and sleep continuity (awakenings). airflow. In addition. The conference participants noted that requiring patients to discontinue ongoing treatment. it may not be an accurate measure of sleep latency. clinically significant MDD and anxiety disorder. duration of sleep. parental completion of sleep diaries is also appropriate. Self-report measures may be appropriate in some studies. PSG remains an important screening tool and can also provide a more complete picture of sleep architecture at important clinical end points. Sleep diaries. conducted in an unfamiliar environment with multiple physiologic sensors. the ever-changing clinical status of the patients. the PSG procedure itself. adolescents with DSPS). patients should be evaluated for their primary disorder. either may not be tolerated or may interfere with the child’s usual sleep. Although home-PSG equipment is beginning to be used by some research centers. alcohol and substance abuse). as long as their condition is stable and the drug dose is stable for a reasonable period of time. however. have been shown to be reliable in comparison to actigraphy. The most common tools are questionnaires and sleep diaries. thus limiting the sleep study as valid measure of the child’s sleep characteristics. Actigraphy can provide assessment of sleep patterns throughout the study and is less prone to negative laboratory effects. June 2006 e1227 . electromyogram. Furthermore. (eg. Subjective Assessment Pediatric sleep studies have used a variety of subjective reporting tools. It involves recordings of electroencephalogram. Thus. uses a wristwatch-like device that is attached to a patient’s wrist or ankle during a recording period to measure activity as a surrogate for sleep-wake. As a result. restless legs syndrome. electro-oculogram. both PSG and actigraphy will be appropriate and complementary assessment tools to be used at different points during pediatric drug development. because it may be difficult to distinguish quiet wakefulness versus actual sleep. During the first screen. thus. sleep-related breathing disorders. and limb muscle activity. PEDIATRICS Volume 117. Actigraphy provides a significant advantage in that it can easily be conducted at home and. and oppositional defiant disorder. most PSG studies continue to be performed in sleep laboratories. Actigraphy also provides a measure of night-to-night variability and can potentially detect unreported circadian sleep disturbances. less burdensome estimate of usual sleep warrants further investigation. however. Few questionnaires have been validated as measures for pretreatment and posttreatment. Incentives and creative strategies to enhance daily compliance with reporting may be important. All were endorsed as relevant exclusions for pediatric trials. Given the populations under consideration. Inclusion and Exclusion Criteria A 2-tiered set of inclusion criteria for trial participation eligibility was endorsed by conference participants. oxygen saturation. These include exclusion of other sleep disorders that may be associated with insomnia symptoms (eg. Actigraphy. that some children. There is concern. may provide a more natural view of patient sleep.because of the high likelihood of drug-drug interactions that would confound the results. The option of in-home PSG recordings as a more acceptable. that can cause sleep disruption. and periodic limb movement disorder) and other conditions (eg. such as obstructive sleep apnea. including conduct disorder. such as for ADHD. discontinuation of these medications would create study conditions that do not adequately mirror the actual situation in which insomnia therapies would be prescribed. activity-based sleep monitoring. but excessive sensor loss in an unattended setting may limit this approach. Appropriate exclusion criteria recommended by all of these workgroups were similar to standards used in most adult sleep studies. especially in the PDD or ADHD clinical populations. PSG will be an important diagnostic step in clinical trials for insomnia treatment to screen for other sleep disorders.

and elimination profiles specific for pediatric populations and that appropriate dosing is selected for clinical trials. metabolism. clinical trials should include both behavioral and pharmacologic therapy (singly and in come1228 MINDELL et al bination) to understand the most effective treatment combinations for each group of patients. late-night television viewing. graduated extinction (combining extinction with parental checks of the child). Because the disorders suggested for study are chronic disorders. Since 1977. and children have been less responsive. and sprinkle) that are easy to swallow and that have an agreeable taste. including the likelihood of significant individual variation in response to medication and difficulties estimating sample sizes given our limited knowledge of effect sizes for medications for pediatric insomnia. Ideally. because of their underlying neurobehavioral abnormalities. Statistical Issues A consideration of statistical issues is instrumental in the development of pediatric hypnotic clinical trials. longer-term studies should be considered (3– 6 months). when appropriate. All of the families participating in clinical trials should receive basic information of positive sleep practices in children and adolescents.Primary Disease Outcomes Small studies have shown both improvements in daytime functioning and reductions in symptomatology when children with insomnia and ADHD or PDD were treated for sleep disturbances. Thus. suspension.and multipledose pharmacokinetic studies covering appropriate age ranges to ensure that the compounds under evaluation have well-understood absorption. require that children participating in clinical research be subject to only minimal risk unless there is prospect of direct benefit. codified as “The Common Rule. Ethical Considerations Clinical trials involving children and adolescents require a high degree of sensitivity to ethical issues involved in research. The pediatric population covers a broad range of ages and body weights with a corresponding range in ability to metabolize pharmaceuticals.54 A federal panel. or age-inappropriate sleep-wake schedules. the Secretary’s Advisory Committee on Human Research Protections. Methodologic Issues Dose Definition All of the participants agreed on the need for clinical trials to determine safe and efficacious doses of hypnotics in children and adolescents. including crying. This diversity necessitates single. Many children have difficulty swallowing pills. study designs should include a mechanism for measuring drug discontinuation effects either through a placebo run-out phase or other appropriate follow-up mechanism. recommendations for research involving children from the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. the most common formulation of adult medication. Children may be exposed to a “minor increment over minimal risk” in research that offers no direct benefit but is “likely to yield generalizable knowledge about the subject’s disorder or condition. Subpart D. until morning).” Minimal risk is defined as “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological tests. However. having significant impact on resolving behavioral insomnia. For children with ADHD. An additional concern is the formulation in which medications would be studied. In addition. these findings are mostly supported by anecdotal clinical evidence.” The definitions of “minimal risk” and “minor increment over minimal risk” are imprecise. Study Duration and Discontinuation Effects Studies should be conducted using a duration that is appropriate for the target population of each study. Behavioral Therapy Behavioral therapy can be extremely effective in some forms of pediatric insomnia. has been reviewing Subpart D and has . The consensus recommended against the inclusion of primary disease outcome measures. Unfortunately. Another issue of concern will be the potential for heterogenous participant populations resulting in significant variability in pretreatment baseline data. and parent education about pediatric sleep are empirically supported treatments. Instead. There are a multitude of issues that will need to be considered. Requiring an insomnia therapy to demonstrate a positive impact on a condition other than insomnia would be an unreasonably difficult hurdle to pass and would set a new precedent beyond the current accepted scope of the drug development process. and there has been significant discussion recently regarding this issue and what defines more than minimal risk. and in some conditions it is preferable to pharmacologic treatment. distribution. it is recommended that a child should not be required to complete and fail a course of behavioral therapy before becoming eligible to participate in a clinical trial. behavioral interventions have been more difficult to implement. pediatric medication should be available in acceptable or multiple formulations (eg. syrup. Studies have shown that extinction (putting the child to bed and ignoring inappropriate behavior. it should be noted that basic sleep-promoting practices should be in place to ensure that the insomnia is not related to such factors as caffeine use.” 45 CFR 46.

More extensive. and many are unable to provide informed consent. regulators. Evidence exists that treating sleep disturbances may have a positive impact on aspects of a comorbid disorder. rigorous studies are needed to characterize the type and degree of improvement for each patient population. June 2006 e1229 . Improving Diagnostic and Assessment Tools Additional research focusing on diagnostic and assessment tools for sleep disorders in children are needed. These gaps in the current understanding of childhood insomnia can help define a research agenda to better characterize the disorder. young children tend to demonstrate hyperactivity. Characterizing the Population Few. it is important to remember the need for 2 sets of tools: one measuring the child’s sleep disturbance and a second tool measuring the impact on family functioning. As a result. A significant number of children with PDDs are nonverbal. such as autistic disorder and Asperger’s disorder. relatively small-scale studies of the prevalence of childhood insomnia in population-based samples have been conducted. comorbidities. participants agreed that studies of the safety and efficacy of pharmacologic treatment of insomnia in children and adolescents are needed. little knowledge of the true frequency of occurrence. and improve treatment options. Two related topics in the pharmacologic management of pediatric insomnia include: (1) ensuring that drug research focuses on the well-being of the child and the family. Although caregivers are legally responsible for informed consent for all children. It is important to restate the point that few studies have been conducted on pharmacologic management of pediatric insomnia. but this will be a more sensitive issue with some of the recommended study populations. Insomnia is somewhat unique among childhood ailments in that reports of the condition reflect the caregiver’s perception of normal childhood sleep patterns. and developmental factors and pediatric insomnia. obtaining assent from children is something that always needs to be managed with pediatric populations. the necessary cautions and safeguards become even more important with this group of children because of their diminished capacity to provide consent. including ADHD and depression. Number 6. whereas teenagers are more likely to be sleepy during the day. not only those actively presenting with pediatric insomnia. as well as appropriate ways to assess daytime functioning in children. either to their parents or investigators. Investigations of these modified scales could enhance the value of information resulting from pediatric clinical trials. Unanimously. and (2) data safety monitoring boards in pediatric clinical investigations be used routinely. validated adult insomnia subjective measurement tools could potentially be modified to reflect the different symptoms present in younger patients. Daytime consequences of insomnia vary across age groups. ultimately providing guidance to clinicians on the relative importance of treating sleep problems in patients undergoing treatment for another disorder. especially children with PDDs. as well as feedback. Distress experienced by the child’s parent or the family may be significant but is not an appropriate motive for exposing a child to pharmacologic therapy. for example. Rigorous large-scale clinical trials will offer greatly needed information on the safety and effiPEDIATRICS Volume 117. This population is frequently prescribed pharmacotherapy lacking evidence for efficacy or safety. and investigators on the opportunities and challenges involved in developing clinical trials for pediatric insomnia. A final ethical issue is the high likelihood of diminished capacity for consent in some of these populations. When developing tools for pediatric research. To this end. As a first step. resulting in important knowledge gaps. there was agreement that studies should be confined to children with clinically measurable evidence of insomnia. Many questions also remain about potential linkages between cultural. identify valid assessment tools. socioeconomic.drafted more explicit guidelines for stratifying risk. Summary A 2-day conference was convened to achieve consensus recommendations on the pharmacologic management of insomnia in children and adolescents. and consequences of pediatric insomnia exists. however. causes. Conference participants endorsed the use of data safety monitoring boards responsible for ensuring the safe conduct of any study. although the basic categories of research permitted in children will likely remain unchanged. Clearly. Most research has focused on individuals whose families have actively sought treatment for pediatric insomnia or another primary disorder with comorbid insomnia. There was concern on the part of both the Food and Drug Administration and clinician participants that research for drug development should be concentrated on treating the child. Population-based studies could provide valuable insights into these questions and establish the basis for future recommendations for standard guidelines for pediatrician interaction with all children. ethnic. Recent concerns about the difference between safety profiles of the selective serotonin reuptake inhibitors in children relative to adults has highlighted the potential dangers of low-frequency adverse effects unique to children. Research Needs and Recommendations The consensus recommendations discussed in this article are intended to provide guidance to sponsors. This complicates the development of assessment tools.

consolidation. Carol L. MD. and Thomas Roth. Children’s Hospital of Philadelphia (Drs Meltzer and Mindell). PhD. Offering education about age-appropriate good sleep practices and. PhD. MD. Second. because this would provide a distorted view of actual usage conditions in the conditions most likely to benefit from this therapy. the use of concomitant medications should not be an exclusion criterion. Anna Ivanenko. MD. MD (cochairs). Myron Genel. Inc. Glaze. Witmans. MD. Author and Contributor Affiliations Altos Pediatric Associates (Dr Babcock). Conference Sponsors King Pharmaceuticals. Lisa Mathis. and Mr Steinitz). and Graham Emslie. Daniel Glaze. MD. APPENDIX Writing Group Members Jodi A. University of Chicago (Dr Kohrman). Mindell. Frank Steinberg. improvement in PDD and ADHD disease outcomes should not be considered as primary study outcomes for insomnia but should be used with care in clinical research and used only as secondary drug development outcome measures. Sanofi-Aventis (Drs Gayda and Thacker). Sepracor (Ms Kirk and Dr Wessel). Food and Drug Administration (Drs Grylack. MD (co-chairs). The Children’s Hospital–Boston (Dr Ferber). MD. and Rappaport). State University of New York Stonybrook (Dr Carlson). University Hospital of Cleveland (Drs Blumer and Rosen). Inc. MD (chairs). Workgroups Workgroup I: Medical/Behavioral/Primary Sleep Disorders Carol L. MD. Miami Children’s Hospital (Dr Padilla). and independent consultant (Dr Steinberg). Workgroup III: Neurologic Jeffrey Blumer. was recommended as a desirable addition to clinical trials of any pharmaceutical compound. Yale University (Dr Genel). PSG and actigraphy were both endorsed as useful tools to examine clinically relevant outcomes for insomnia. Inc. Glaze. Organon (Drs Igvy May and van Den Berg). Pfizer (Ms Tufts and Dr Wang). Kyle Johnson. DO. Mr Drobnich. Conference Organizers National Sleep Foundation and Best Practice Project Management. PhD. PhD. University of Texas–Southwestern (Dr Emslie). Rosen. Speakers Jeffrey Blumer. Sepracor. National Sleep Foundation (Mr Pritz. Conference Cochairs Jodi Mindell. PhD. Graham Emslie. Pfizer. Baylor College of Medicine (Dr Glaze). duration. Mr Sears. PhD. Medical College of Wisconsin (Dr D’Andrea). PhD. which are improving total sleep time. University of Alberta (Dr Witmans). Workgroup II: Psychiatric Anna Ivanenko. and Daniel G. Daniel G. MD. MD. Myron Genel. Mr Gelula. and Kyle Johnson. Oregon Health and Science University (Dr Johnson). decreasing wake time after sleep onset and number of night wakings. MD. MD. as well as behavioral interventions. shortening sleep onset delay. Finally. patients with either comorbid PDD or ADHD were endorsed as appropriate groups for initial research. Mathis. The first key point of agreement was the endorsement of a definition of pediatric insomnia as “repeated difficulty with sleep initiation. SanofiAventis. possibly. Carol L. National Centers on Sleep Disorders Research (Dr Hunt). evaluation of behavior in general. MD. National Institutes of Mental Health (Dr del Carmen-Wiggins and Dr Lederhandler). MD (cochairs). Kyle Johnson. MD. and eliminating early morning wakings that result in insufficient sleep. MD. Furthermore. Johns Hopkins University (Dr Riddle). Jeffrey Blumer. and Takeda Pharmaceuticals North America. and Manisha B. MD. Bridget Banas. McNiel. Ms McKenna Luz. or quality that occurs despite age appropriate time and opportunity for sleep and results in some form of daytime functional impairment for the child and/or family. Loyola University Medical Center (Dr Ivanenko). Rosen. Thomas Roth. Agreement on study design included consensus on the need for pharmacokinetic and pharmacodynamic studies to determine appropriate doses and safety profiles before larger-scale clinical trials. providing these patients a better night’s sleep. Consensus was achieved on the major methodologic questions addressed during 2 days of deliberation. Best Practice Project Management (Dr Meyer). . Anna Ivanenko. Inc. MD. especially because these groups commonly receive pharmacotherapy for insomnia. MD. Henry Ford Hospital (Dr Roth). Rosen. National Institute of Nursing Research (Dr Koepke). PhD. King Pharmaceuticals (Ms Jacksland and Dr James). and Graham Emslie. Jodi Mindell. PhD. MD.cacy profiles of sedative/hypnotics.” Entry criteria for the duration or chronicity of the problem of insomnia may differ from study to study but should be specified a priori. PhD. e1230 MINDELL et al PhD. Takeda Pharmaceuticals (Dr Weigand). Organon.

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