The Elephant in the Nursery; Different Perspectives on Insomnia in Children

1. The Elephant in the Nursery; Different Perspectives on Insomnia in Children Judith A. Owens MD MPH Children’s National Medical Center Washington DC Northeastern Sleep Society Annual Meeting April 2011

2. In the past 12 months, I have had the following financial relationship with the manufacturers of commercial products: • Eli Lilly (Speakers Bureau) • Shire (Speakers Bureau, Research grant) • Rhodes Pharmaceuticals (Consultant) • Takeda (Consultant) • Shionogi Pharma (Consultant) • Cephalon (Consultant) • Neuropro (Consultant) • Transcept (Consultant) • Isis Biopolymer (Advisory Board) • Off-label drugs will be discussed Disclosures

3. Objectives Review controversial issues regarding insomnia in children: Definitions Cultural considerations Behavioral interventions Pharmacologic treatment

4. What is “Pediatric Insomnia”? Descriptive, not diagnostic term Dependent on parental recognition/definition Multiple possible medical/behavioral etiologies for same constellation of symptoms Occurs in evolving developmental context Treatment should be diagnostically-driven Evaluation is key

5. Consensus Definition • Repeated difficulty with sleep initiation, duration, consolidation, or quality • Viewed as problem by the child and/or caregiver • Occurs despite age-appropriate time/opportunity for sleep • Results in daytime functional impairment for the child and/or family • Significance of the sleep problem determined by: • Severity, chronicity, and frequency of behavior • Child and parent variables • Cultural considerations

6. Clinical Definition • Bedtime refusal or resistance • Delayed sleep onset • Prolonged night wakings • Or some combination • Requires parental intervention

7. DSM-IVR Primary Insomnia Insomnia related to another mental disorder Associated with general medical condition or substance abuse ICSD II Behavioral Insomnia of Childhood Sleep onset association Limit setting Psychophysiologic Adjustment Idiopathic Associated with mental disorders, medical conditions or medications Pediatric Insomnia: Diagnostic Classification

8. Proposed DSM V Insomnia Disorder A. The predominant complaint is dissatisfaction with sleep quantity or quality made by the patient (or by a caregiver or family in the case of children or elderly). B. Report of one or more of the following symptoms: -Difficulty initiating sleep; in children this may be manifested as difficulty initiating sleep without caregiver intervention -Difficulty maintaining sleep characterized by frequent awakenings or   problems returning to sleep after awakenings (in children this may be manifested as difficulty returning to sleep without caregiver intervention) -Early morning awakening with inability to return to sleep -Non restorative sleep  -Prolonged resistance to going to bed and/or bedtime struggles (children)

9. Proposed DSM V Insomnia Disorder C. The sleep complaint is accompanied by significant distress or impairment in daytime functioning as indicated by the report of at least one of the following:  -Fatigue or low energy -Daytime sleepiness -Cognitive impairments (e.g., attention, concentration, memory) -Mood disturbance (e.g., irritability, dysphoria) -Behavioral problems (e.g., hyperactivity, impulsivity, aggression) -Impaired occupational or academic function -Impaired interpersonal/social function -Negative impact on caregiver or family functioning (e.g., fatigue, sleepiness

10. Proposed DSM V Insomnia Disorder D.   The sleep difficulty occurs at least three nights per week. E.   The sleep difficulty is present for at least three months. F.   The sleep difficulty occurs despite adequate age-appropriate circumstances and opportunity for sleep. Duration:  1.    Acute insomnia (<1 month) 2.    Sub acute insomnia (1-3 months) 3.    Persistent insomnia (> 3 months) Clinically Comorbid Conditions: -Psychiatric disorder (specify) -Medical disorder (specify) -Another disorder (specify)

11. Behavioral Insomnia of Childhood: ICSD-II Definition • Sleep Onset Association subtype • Falling asleep is an extended process that requires special conditions • Sleep-onset associations are highly problematic or demanding • In the absence of the associated conditions, sleep onset is significantly delayed or sleep is otherwise disrupted • Nighttime awakenings require caregiver intervention for the child to return to sleep

12. Behavioral Insomnia of Childhood: ICSD-II Definition • Limit Setting subtype • The child has difficulty initiating or maintaining sleep • The child stalls or refuses to go to bed at an appropriate time or refuses to return to bed following a nighttime awakening • The caregiver demonstrates insufficient or inappropriate limit setting to establish appropriate sleeping behavior in the child

13. Sleep issues are defined as “problems” in young children because they disturb parental sleep Clinicians “pathologize” night wakings Disrupted sleep is problematic due to direct negative consequences on child mental and physical health Caregiver sleep disruption increases family stress and compromises parenting Clinicians respond to legitimate parental concerns Pros and Cons

14. Sleep and Culture: Differences and Similarities • Sleeping environment • Infant sleep practices (bed-sharing/cosleeping, sleeping position) • Napping patterns • Bedtime rituals, transitional objects

15. What is Cosleeping? • The practice of having an infant or young child share a sleeping space with mother and/or father (caretaker) • Types: • Isolated (extraordinary circumstances) • Occasional >1x/mo, <3x/wk vs frequent or habitual >=3x/wk • All night/ part-night • Room-sharing, proximate, bed-sharing • ”Reactive” vs “lifestyle” cosleeping distinction

16. Why Look at Culture? • Eastern vs Western beliefs in bed-sharing • Very high acceptance and rates of co-sleeping in Asian societies • Relatively less value placed on development of independence in young children • Family interdependence vs individual autonomy

17. Infant sleep problems result from “Westernization” of traditional sleeping practices Solitary sleep is at best impractical and at worst psychologically harmful to the child Cosleeping is the optimal sleeping arrangement The transition to “solitary sleep” is a natural reflection of societal changes Cosleeping may be associated with more fragmented and less deep sleep, increased stress response and more sleep problems Cosleeping is a lifestyle choice Pros and Cons

18. Behavioral Interventions for Insomnia: Definitions • Extinction • Bedtime fading • Positive routines • Scheduled awakenings • Positive reinforcement • Parental education

19. Extinction • Elimination of parental attention as a reinforcer for undesired behaviors (e.g., crying) • Unmodified extinction (“cry it out” or “cold turkey” approach): parents put the child to bed at a designated bedtime, and then ignore protest behaviors such as tantrums until a preset time the next morning • Effective but poorly tolerated by many parents • Variations include parent sleeping in child's room, in separate bed, while carrying out systematic ignoring

20. Extinction • Graduated extinction (“sleep training, checking, controlled crying, Ferber method”): variety of techniques in which parents are typically instructed to ignore bedtime crying and tantrums for specified periods of time • Involve gradual shaping of appropriate behaviors and fading of interventions

21. Treatment Issues • Common for crying/protest to briefly intensify 2nd or 3rd night (“extinction burst”) - vomiting • Avoid intermittent reinforcement (the “lottery theory”) • Avoid increasing reinforcement during checks • Do not allow child to extend day sleep • Improvement in one week if parents consistent • Easier to accomplish before child developmentally able to climb out of crib or has been transitioned to a bed

22. Variations on Graduated Extinction • Parent stays with child at sleep onset, gradually fades attention, assistance, and presence • Parent sits in chair at sleep onset, gradually moves chair out of room • Parent sleeps beside child’s bed, gradually moves bed out of room • Child allowed to sleep on separate bed in parent’s room during night wakings • Bedtime pass

23. Behavioral Treatment of Bedtime Problems and Night Wakings in Infants and Young Children * • Review of 52 studies • Behavioral treatment produces clinically significant, reliable, and durable changes (80% of children improve) • Positive effects on secondary outcome variables • Child-related, such as daytime behavior • Caregiver-related, such as parental well-being • 94% of studies report intervention was efficacious • Adverse secondary effects not identified in any studies * AASM Standards of Practice Committee Review Mindell et al., Sleep, Oct 2006

24. AASM Practice Parameters* • Standards • Unmodified extinction • Extinction with parental presence • Parental education • Guidelines • Graduated extinction • Bedtime fading/positive routines • Scheduled awakenings *Morgenthaler et al, Sleep, Oct. 2006

25. Behavioral interventions “teach” parents to ignore their crying/distressed child Behavioral interventions may be viewed as “neglect” Treatment may compromise infant-parent attachment security Behavioral interventions regulate how quickly and appropriately parents respond to crying Successful treatment improves infant and caregiver sleep and well-being Beyond short-term distress, negative consequences have not been identified Self-soothing is the first step in the development of self-regulation Pros and Cons

26. Medications for Insomnia • 25% of first-born infants had been given “sedatives” by 18 months (Ounstead, 1977) • 35% of prescriptions in < 1yr olds for sleep disturbances; 23% 2-5 yr olds; most common type drug therapy;chlorpromazine most frequent (Trott, 1995) • 49% of pediatricians reported recommending OTC antihistamines, 15% prescription antihistamines for sleep in 0-2 yo (Owens,

27. Pediatric Survey: Prescription Medications for Insomnia

28. Child Psychiatry Survey: Prescription Medications for Insomnia* Percent of respondents prescribing *In a “typical” month Owens et al 2010

29. Medication Use: General Principles Medication rarely first choice or sole treatment strategy Optimize sleep hygiene Combine with behavioral therapy: increased long-term efficacy and decreased side effects Treatment selection based on clinical assessment of best possible match between clinical situation and drug properties Treatment goals: realistic, clearly defined, measurable agreed upon by caregivers have plan for follow-up Initiate lowest dose; titrate as needed Shortest possible duration of therapy

30. Medication Use: General Principles Selection of appropriate meds short-acting meds for sleep onset longer-acting meds for sleep maintenance minimize “am hangover” Timing of administration Hypnotic vs chronobiotic (melatonin) “Forbidden zone” of circadian alertness Side effects reviewed with family Frequent monitoring efficacy, side effects Avoidance abrupt discontinuation (rebound)

31. Medication Use: Safety Issues Screen adolescents for alcohol/drug use, pregnancy Screen for use OTC sleep meds Assess possible drug-drug interactions (PK/PD) “Paradoxical” effects Exacerbation co-existing sleep disorders (ie, SSRIs/RLS, risperidone/OSA) Contraindications: Insomnia occurs in presence of untreated primary sleep disorder (SDB, RLS, DSPD) Insomnia due to developmentally-based normal sleep behavior Insomnia due to self-limited condition Potential drug interactions/substance use Limited ability to monitor meds

32. Little empirical data: case reports/series • Few pediatric randomized controlled trials • Extrapolation adult data • Clinical experience guides usage There are currently no sleep medications labeled for use in children by the FDA

33. Diphenhydramine: Pediatric Studies DB RCT 50 children 1mg/kg: subjective improvement SOL, NW1 “TIRED” study2 Design: 44 6-15 month olds with night wakings 1-week DB, PC RCT; f/up 2,4 wks Outcomes: parent-reported decrease night wakings requiring assistance, improved sleep, parental satisfaction sleep, SOL Results: 1/22 DPH vs 3/22 improvement Data safety monitoring board stopped trial due to lack of efficacy 1Russo 1976 2Merenstein 2006

34. Melatonin: Pediatric Studies Increased duration and/or quality of sleep in special needs (eg, blind, MR, Rett syndrome, Angelman’s) children with irregular sleep-wake patterns and phase delay1: Effects variable across individuals Generally well-tolerated Some improvement daytime functioning No long-term data efficacy, safety 1Malow 2008

35. Melatonin: Pediatric Studies (ADHD) Premise: Children with ADHD have a delayed endogenous circadian clock ADHD patients with sleep onset insomnia vs normal controls have significantly later sleep onset, morning wake time, melatonin onset Several studies suggest 5 mg bedtime melatonin significantly shortens SOL in children with ADHD1-4 1-2Smits et al 2001, 2003; 3-4Van der Heijden et al 2005, 2007

36. Melatonin: Pediatric Studies (ADHD) 27 ADHD patients treated sequentially with “sleep hygiene” (consistent bed/wake time, avoidance of caffeine, naps) and melatonin 5 mg QHS or placebo1 5 patients “sleep hygiene responders” (SOL  60 minutes) Sig reduction mean SOL 98 minutes to 73 minutes CGI sleep no change in 54% Melatonin vs placebo (crossover design) Sig reduction mean SOL 16 minutes No difference in night-to-night variability, sleep duration, CGI sleep, ADHD ratings 90-day open-label trial with melatonin treatment responders Mean SOL 31 minutes Sleep duration increased 23 minutes 1Weiss 2006

37. NBzDRAs: Pediatric Studies Case study 7yo ASD: reduction SOL Zolpidem trial; DB/PC/parallel design1 N=201; ADHD –related insomnia 0.25mg/kg – max dose 10mg No significant change mean change SOL week 4 drug vs placebo; improved CGI 12-17yo No residual sedation/rebound Side effects: dizziness, headache, hallucinations; 7% discontinuation due to AEs Children may require dose > adults 1Blumer 2009

38. Clonidine: Pediatric Studies Retrospective chart review 62 pts1 Improvement medication-induced/exacerbated, baseline sleep disturbance AE’s in 31%; mild (am drowsiness) Description of clinical experience 100 pts2 Rapid onset action; all-night duration (30 minutes) Parent-reported improvements sleep, ADHD No adverse events Adequate clinical response, low side effect profile3 Caveats Reports sudden death in combination with stimulants4 Increase in ER reports clonidine toxicity5 1Prince 1994, 2Wilens et al 1995 3Ingrassia 2005 4Popper 1995 5Kappagoda 1998

39. Case 1: “She’s going to put me in the hospital” • Four year old girl difficulties maintaining sleep • SH:38 yo single mother - 8th grade education, hx of sexual/physical abuse, depression, PTSD, previous psych hospitalizations • FH:Mother, mat GM “insomnia” • Med:Mother on methadone during pregnancy • Dev: Child is “2 years behind in everything” ?ADHD, temper tantrums, aggressive

40. Case 1 • Bedtime 9p; actual sleep onset “10p-1a”; frequent “curtain calls”; needs mother in room to fall asleep • Night wakings frequent on sleep diary • 11p: “wanted to eat ice cream” • 1a, 3a: “put TV on” • 5a: “had some milk”; fell asleep mother’s bed • Previous treatment: • Diphenhydramine qhs: “it stopped helping” • Alpha agonist qhs discontinued due to side effects (increase parasomnias): “the pills helped more than you know” • Current status: “I can’t take this anymore; I’m afraid of what will happen”

41. Differential Diagnosis of Bedtime Resistance/Night Wakings in Young Children • Behavioral Insomnia of Childhood: • Sleep Onset Association subtype • Limit Setting subtype • Combined • Sleep disorders related to medical conditions • Environmental factors • Inadequate sleep hygiene • Medications

42. Evaluation of Bedtime Resistance/Prolonged Sleep Onset Assess for Inadequate Sleep Hygiene Anxiety symptoms Sleep onset in relation to bedtime Chronic medical or psychiatric conditions Primarily bedtime-related Daytime and bedtime Falls asleep easily at later bedtime Consistent prolonged sleep onset Generalized Anxiety Disorder Leg sensations relieved by movement, +FH Restless Leg Syndrome Assess parent-child interactions, child behavior Anxiety falling or staying asleep Primary insomnia Dream-related anxiety Nightmares Developmentally-appropriate fears Nighttime Fears Youngerage    Older age Parental presence needed to sleep; nightwakings Sleep Onset Association Disorder Bedtime refusal, delaying tactics; no or few nightwakings Limit-Setting Sleep Disorder Developmentally Inappropriate bedtime Circadian preference Delayed Sleep Phase Syndrome

43. Case 1: Key Points • Role of psychosocial factors and neurodevelopmental issues in the decision to use (or not use) a hypnotic • Impact of previous drug therapy • Role of behavioral management; how likely is behavioral management alone to be successful?

44. What would you do first? • Institute sleep hygiene and behavioral interventions (graduated extinction, bedtime fading) • Restart clonidine 0.05 mg qhs • Defer treatment and refer to a child psychiatrist for evaluation of ADHD

45. Case 2: A Child with Special Needs • 8 year old boy with autism spectrum disorder and the following sleep complaints: • Delayed sleep onset with time to fall asleep > 90 min • Active parental involvement at bedtime, rigid bedtime routines • Prolonged and disruptive nightwakings lasting on average 40-90 minutes almost every night • Early and irregular morning waketimes >2x/week • Irregular sleep/wake schedule with prolonged daytime naps during inappropriate time of day (late afternoon) • Frequent co-sleeping • Non-verbal, moderate MR, intermittently aggressive, self-stimulatory behaviors

46. Differential Diagnosis of Sleep Problems in ASD • Chronobiological: • Circadian rhythm abnormalities • Disturbance in melatonin production in autism • Less entrainment by social/environmental cues • Primary arousal dysfunction; ?altered homeostasis • Sensory issues • Psychosocial • Learned maladaptive sleep patterns • Anxiety-related; high levels autistic children • Inadequate parent limit-setting • Parents may be more aware of difficulties than parents of typically developing children • Parents may see sleep problems as “inevitable” and therefore untreatable • Many patients have more than one etiology • Some patients may have more than one sleep disorder

47. Case 2: Key Points to Consider • Chronicity and severity of sleep disorder • Sleep onset and maintenance issues • Role of underlying CNS abnormalities • Impact on family • Impact of daytime functioning • Family’s goals

48. What would you do first? • Initiate trial of melatonin 3 mg at bedtime • Institute light box phototherapy in am • Initiate trial of sedating atypical antipsychotic (eg, risperidone) qhs • Institute sleep hygiene and behavioral interventions (graduated extinction, bedtime fading) • Initiate trial of controlled-release non-BZD receptor agonist

49. Pharmacological treatment Melatonin qhs Multiple medications used clinically (eg, alpha agonists, antidepressants, atypical antipsychotics, anticonvulsants) Circadian-based interventions Chronotherapy AM bright light Sleep hygiene Behavioral management Bedtime routines Extinction procedures Bedtime fading Occupational therapy Brushing Weighted vests, blankets Sleep environment Safety issues Treatment Strategies

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