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That a child needs proper sleep and longer hours of sleep than an adult is such a well recognized fact among common-sense people that it seems strange it should be still necessary to preach it out to the public. Nature March 18, 1909

Introduction

Sleep is one of the most discussed topics during a child visit [1].

  • Identification and treatment of sleep problems in children is important since a growing body of evidence suggests a link between sleep disorders and physical, cognitive, emotional, and social development.

  • Different epidemiological studies indicate that up to 50 % of children experience a sleep problem [2–4], and about 4 % have a formal sleep disorder diagnosis [5].

  • The presentation, natural history, and response to treatment of insomnia may differ considerably between adults and children, and even within the pediatric age group, the clinical manifestations of sleep problems may vary by age and developmental level.

Prevalence of Insomnia

About 20–30 % of children under the age of 3 years were reported by parents as problematic for bedtime difficulties and frequent night wakings [6] that tend to persist in a large percentage of children [7].

There is a large data variability that is related to study methodology, definition of insomnia, and inclusion criteria (parental report of problematic sleep or strict definition of insomnia as more than three awakenings per night, and sleep latency higher than 30 minutes).

For parents of infants and toddlers, night awakenings are the most common sleep complaints, with 25–50 % of children older than 6 months of age continuing to awaken during the night. Bedtime resistance is found in 10–15 % of toddlers. A recent longitudinal study in the first year of life showed that about 10 % of the infants were reported by parents as having a problematic sleep. Approximately 50 % of infants had an average of 1–2 awakenings per night, while >2 awakenings were present in 9 % at 3 months, 21 % at 6 months, 26 % at 9 months, and 17 % at 12 months.

Infants with >2 nighttime awakenings slept more often in the parent bed than infants without awakenings, at 3 months and 9 months. From this study also emerges that parental perception of sleep problem at all ages significantly correlated with nocturnal awakenings and difficulties falling asleep [8].

Difficulties falling asleep and night wakings are also common in preschoolers (15–30 %). In older children the main insomnia symptoms reported are sleep-onset difficulty (15 %) and sleep-related anxiety (11 %) [9].

The majority of adolescents sleep less than recommended on school nights and suffer from chronic sleep deprivation [10]; the tendency to delay sleep onset results in bedtimes that are too late to permit habitually sufficient nighttime sleep, and evening-time use of electronic devices such as computers, smart phones, televisions, or video games can delay bedtime or contrast melatonin secretion resulting in delayed sleep onset even after cessation of the activity; moreover, consumption of caffeinated beverages is another contributing factor that can disrupt sleep hygiene resulting in poor sleep quality [11–13].

The exact rate of insomnia among adolescents is uncertain [14]: 20–26 % of adolescents took more than 30 min to fall asleep [15].

A high prevalence of insomnia ranging from 23.8 to 18.5 to 13.6 % was found most pronounced in girls than boys [16].

A recent study showed that adolescent sleep generally declined over 20 years with the largest change occurred between 1991–1995 and 1996–2000 [17].

A clear approximately twofold increasing trend in insomnia symptoms and tiredness was found from the mid-1990s to the end of the 2000s, but after 2008, the increase seems to have stopped. Insomnia symptoms and tiredness were associated with lower school performance, and they were more prevalent among girls (11.9 and 18.4 %) compared to boys (6.9 and 9.0 %, respectively) [18].

Sleep patterns of adolescents between 16 and 19 years were characterized by late bedtimes, long sleep latency, and short sleep duration, contributing to a daily sleep deficiency of about 2 h on weekdays, including a sleep-phase shift to later bedtimes during weekends [15, 19].

Declines in self-reported adolescent sleep across the last 20 years are concerning since chronic insufficient sleep in adolescents has been associated with declines in school and occupational performances; decreased attention and altered regulation of impulses; the use of caffeine, alcohol, stimulant meds, cannabis, and other drugs; increased risk-taking behaviors; depression; suicide ideation; and somatic health and psychological problems [20].

In general, the total sleep duration of children and adolescents seems to be decreasing over time compared with previous generations [21], and the reason why children and adolescents are getting less sleep is in part related to changes of social habits.

Environmental and psychosocial factors such as the increased use of electronic media have a considerable influence on the amount of sleep obtained by children and adolescents.

The intrusion of technology in the sleep of children and adolescents is an emerging problem. It should be taken into account that mobile telephone technology has evolved at such a rate that children and adolescents now use their mobile telephone to access the internet, send and receive emails, engage in social networking, listen to music, and play games [22]. Among a range of technologies, interactive technological devices are most strongly associated with sleep complaints [23].

A recent research comparing preadolescents and adolescents sleep pattern in relation to the use of technology showed that adolescents reported more sleep problems, more eveningness, increase of Internet, social network and phone activities, while preadolescents were more involved in gaming console and TV. The transition from preadolescence to adolescence should be considered at high risk for the development of sleep problems and bad sleep habits. Therefore, it is extremely important to focus on the preadolescence period to inform about the risks related to the use of technology at bedtime in order to prevent sleep problems in adolescence [24, 25].

Apart from the environmental factors (i.e., technologies), some studies highlighted also the influence of cultural background, since prevalence of insomnia varied greatly in relation to the different countries: for example, sleep problems ranged from 10 % in Vietnam and Thailand to 25–30 % in the United States and Australia and even 75 % in China and Taiwan [26].

Specific pediatric populations have an increased incidence of insomnia, especially children with neurodevelopmental and chronic medical and psychiatric conditions [9, 27, 28].

Consequences of Insomnia

Several data from the literature indicates that pediatricians and parents should be aware of the consequences of insomnia in infants, children, and adolescents:

  1. (a)

    Longitudinal studies have demonstrated that sleep problems often persist throughout childhood and adolescence [11, 12, 29–31].

  2. (b)

    Inadequate sleep quality and quantity in children and adolescents is associated with negative functional outcomes, including sleepiness, inattention, and other cognitive and behavioral deficits [32], as well as psychiatric and health outcomes, such as obesity and metabolic consequences [33, 34].

  3. (c)

    Insomnia and sleep disturbances increase the risk of depression, as well as suicide and self-harm behaviors [35–37].

  4. (d)

    There is also a significant impact on families, with negative effects on daytime function and well-being, as well as elevated levels of family stress [38–43].

A recent meta-analysis of 11 longitudinal studies, comprising 24,821 participants, revealed that children and adolescents with short sleep duration had twice the risk of being overweight/obese, compared with subjects sleeping for long duration, providing evidence that short sleep duration in young subjects is significantly associated with future overweight/obesity [44].

Definition of Pediatric Insomnia

Pediatric insomnia represents a complex combination of biological, circadian, neurodevelopmental, environmental, and behavioral variables; insomnia is defined as a persistent difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, and results in some form of daytime impairment [45].

According to the previous ICSD-2 [46], “pediatric insomnia” was defined as a “repeated difficulty with sleep initiation, duration, consolidation, or quality that occurs despite age-appropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family.”

The diagnosis of behavioral insomnia of childhood (BIC) was introduced in 2005 in ICSD-2 as a unique diagnostic entity to emphasize sleep difficulties that result from inappropriate sleep associations or inadequate parental limit setting. The diagnosis of sleep-onset behavioral insomnia was characterized by reliance on maladaptive and inappropriate sleep associations such as rocking, watching television, falling asleep in the parents’ bed, and so forth. The child is usually unable to fall asleep in the absence of these conditions at both bedtime and following nocturnal arousals. Inadequate parental limit setting can also result in a form of behavioral insomnia characterized by sleep-onset delay secondary to a child’s refusing to go to bed or stalling.

The ICSD-3 [45] describes chronic insomnia disorder with no specific pediatric classification; as a consequence, a related unresolved issue is whether the current global classification promotes a generic approach to insomnia therapy that ultimately fails to benefit some insomnia subgroups. The ICSD-3 defines chronic insomnia as “a persistent difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, and results in some form of daytime impairment”

The criteria include the report from patient or parents/caregivers of difficulty initiating or maintaining sleep, early morning awakenings, resistance to go to bed on appropriate schedule, and difficulty sleeping without parent or caregiver intervention.

The nighttime sleep difficulty determined fatigue/malaise; attention, concentration, or memory impairment; impaired social, family, occupational, or academic performance; mood disturbance/irritability; daytime sleepiness; behavioral problems; reduced motivation/energy/initiative; proneness for errors/accidents; and concerns about sleep. The sleep disturbance and associated daytime symptoms occur at least three times per week and should have been present for at least 3 months.

Based on the ICSD-3, there are several issues that should be considered when approaching an infant/child with insomnia [45]:

  1. 1.

    Parents may have unrealistic sleep expectations for their children and predispose them to insomnia by putting them in bed too early or assigning them too much time in bed each night.

  2. 2.

    Child insomnia is often comorbid with difficult temperament or other comorbid medical and psychiatric conditions.

  3. 3.

    There should be risk factors like difficult home situations, safety concerns, caregiver relationship, and domestic abuse that should be considered or excluded.

  4. 4.

    If the children had a current or past history of medical problems, parents may have difficulty setting limits, because of guilt, a sense that the child is “vulnerable,” or concerns about doing psychological harm.

  5. 5.

    Environmental factors such as the child sharing a room with others and cramped living accommodations may contribute to negative sleep-onset associations or poor limit setting.

  6. 6.

    The psychological asset of the parents (especially depressive symptoms) should be always evaluated.

A debated issue is at what age the diagnosis of insomnia could be done: because children are not expected to sleep through the night with regularity until they are 3–6 months of age, 6 months is a reasonable age to first consider a diagnosis of chronic insomnia disorder, unless the sleeplessness is very marked at an earlier age.

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, DSM-5 [47] does not present any classification of sleep disorders specific for childhood; it includes sleep disorders defined according to criteria that are common for children and adults, although, in some instances, they specify developmental features of particular sleep disorders. The DSM-5 integrated pediatric and developmental criteria and also replaced “primary insomnia” with the diagnosis of “insomnia disorder,” a switch to avoid the primary/secondary designation when this disorder co-occurs with other conditions and to reflect changes throughout the classification. Furthermore, it introduced a temporal criterion (more than three “bad nights” a week for the last 3 months). DSM-5 underscores the need for independent clinical attention of a sleep disorder regardless of mental or other medical problems that may be present.

The most apparent change in ICSD-3 is the collapse of all previous chronic insomnia diagnoses into a single chronic insomnia disorder diagnosis.

Based on duration of symptoms, three insomnia diagnostic categories are identifiable: chronic insomnia disorder, short-term insomnia disorder, and other insomnia disorder. These diagnoses apply to patients with and without comorbidities.

“Chronic insomnia disorder” is characterized by chronic sleep onset and/or sleep maintenance complaints with associated daytime impairment and is reserved for individuals whose sleep difficulties exceed minimal frequency and duration thresholds shown to be associated with clinically significant morbidity outcomes. “Short-term insomnia disorder” is characterized by sleep/wake difficulties that fail to meet the minimal frequency and duration criteria of chronic insomnia disorder. Nonetheless, short-term insomnia disorder is associated with clinically significant sleep dissatisfaction or waking impairment.

“Other insomnia disorders” category should be assigned to those rare cases that fail to meet criteria for short-term insomnia disorder, yet are thought to have sufficient symptoms of insomnia to warrant clinical attention.

The ICSD-3 integrates pediatric insomnia into the major clinical diagnosis of “chronic insomnia disorder” and includes parent/caregiver report of sleep disturbances and associated impairments in daytime function in the child and family. In this classification, however, the differentiation into two different categories of insomnia representing the main clinical manifestations is maintained: the sleep-onset association and the limit-setting disorder.

The “sleep-onset association type” is characterized by the child’s inability or unwillingness to fall asleep or return to sleep in the absence of specific conditions (i.e., inappropriate associations), such as a parent rocking the child to sleep, watching television, feeding, and the presence of parents in the room; in the absence of these conditions, sleep onset is significantly delayed, and when the conditions associated with falling asleep are re-established, the child usually resumes sleep relatively quickly.

Because sleep-onset associations are highly prevalent in young children, the phenomenon is defined as a disorder only if (1) the associations are highly problematic or demanding (e.g., extended rocking, car rides); (2) sleep onset is significantly delayed or sleep is otherwise disrupted in the absence of the associated conditions; and (3) caregiver intervention is frequently required to aid the onset or resumption of sleep.

“Limit-setting” issues are characterized by bedtime stalling or bedtime refusal that is met with and reinforced by inadequate limit setting by a caregiver. Sleep problems occur when caregivers institute no or few limits or when limits are instituted inconsistently or in an unpredictable manner, such as when the parents allow the child to sleep in their bed when the child refuses to sleep.

Fear of sleeping alone, being in the dark, or having nightmares may lead some children to demand certain sleep-promoting conditions (the presence of parent in the bedroom) or to repeatedly delay their bedtimes.

Complications may result from the consequent sleep loss and include irritability, mood dysregulation, inattention, and poor school performance, together with increased family tensions with negative feelings toward the child, parental conflicts, and caregiver sleep loss.

Clinical Approach to Pediatric Insomnia

A thorough knowledge of normal sleep ranges and expected developmental changes is required; since children are not expected to sleep through the night with regularity until they are 3–6 months of age, 6 months is a reasonable age to first consider a diagnosis of insomnia disorder, unless the sleeplessness is very marked at an earlier age [45]. However, when sleep difficulties are persistent and pronounced in infants, underlying medical causes should be considered (like sleep-disordered breathing, gastroesophageal reflux, otitis, allergies, pain, etc.) [48].

The physician must be aware that medical insomnia can be aggravated in combination with behavioral insomnia due to the early alteration of sleep quality inducing wrong associations at bedtime: caregivers may eventually do whatever it takes for everyone to get to sleep, facilitating the development of negative sleep associations.

Multiple night awakenings, mainly in the first year of life, may suggest the presence of gastroesophageal reflux (GERD) or food allergies; diurnal hypersomnolence constitutes an important clinical sign, which suggests another possible diagnosis, such as metabolic or endocrinologic disorders [48].

Sleep-related GERD may present with nocturnal awakenings with a sour taste in the mouth or breath, burning discomfort in the chest, and increased nocturnal arousals leading to sleep fragmentation. Other associated symptoms include abdominal pain, regurgitation, cough, feeding problems, failure to thrive, and respiratory problems.

Many chronic pain conditions – including fibromyalgia, rheumatologic disorders, and other causes of musculoskeletal pain, functional abdominal pain, headaches and migraine, cancer, and spasticity-related pain in cerebral palsy – have been linked to both disturbed sleep and daytime fatigue in children and adolescents [49–53].

Assessment

The assessment of sleep and sleep disturbances in children is performed through subjective (i.e., information reported by the child and/or parents, questionnaires) or objective (i.e., measure of motor or neurophysiologic parameters) tools.

Clinical evaluation is the most important part of the process of assessment and diagnosis of insomnia in the pediatric patients.

An important first step is obtaining information regarding the typical/habitual sleep patterns and difficulties. A sleep history obtained from a frustrated, sleepy parent can be vague and inaccurate, with the parent focusing, at times, on the wrong details. For example, parents often describe the child’s sleep pattern only for the most severe or most recent night or period. A more accurate description of the sleep patterns across time can be obtained from a 2-week sleep diary, log, or chart.

It is also important to assess daytime consequences of sleep disruption and comorbid conditions such as depression, anxiety, chronic medical conditions, and other primary sleep disorders.

Physical examination and laboratory assessment may be valuable as well, though they are not always necessary.

The physical examination depends on the medical history, the specifics of the sleep complaint, and the hypotheses generated during assessment, but some aspects are mandatory to evaluate especially if insomnia is comorbid with other sleep disorders: auxologic parameters (obesity or failure to thrive), neurologic examination, abnormal skull or facial features, oropharyngeal crowding, palatal abnormalities, and chest or spine abnormalities.

A number of screening tools have been developed to assist the child healthcare practitioner in assessing for sleep-related disorders and also for insomnia: a quick memory aid to assess sleep is known as BEARS, which provides a comprehensive screening tool usefulness in the primary care setting as well as in the sleep medicine center.

It consisted of different questions regarding bedtime, excessive daytime sleepiness, awakenings at night, regularity/duration, and snoring that could suggest a series of possible diagnoses [54].

Specific questionnaires can be very helpful both in clinical and research settings, to complete sleep history and focus the parents on specific aspects of her child sleep, for example, the Sleep Disturbance Scale for Children [55], the Brief Infant Sleep Questionnaire (BISQ) [56] or the Children’s Sleep Habits Questionnaire [2, 3], or the Pediatric Sleep Questionnaire [57].

Tests including laboratory and radiographic procedures are not routinely indicated in chronic insomnia, and overnight polysomnography is helpful only to exclude other sleep disorders, such as obstructive sleep apnea, sleep-related movement disorders, or parasomnias.

According to American Academy of Sleep Medicine practice parameters [58], PSG is not indicated for the routine evaluation of insomnia, in the context of an insomnia complaint; it is appropriate if the clinical evaluation raises the suspicion of sleep-related breathing disorders and periodic limb movements.

Actigraphy, although not regarded as a replacement for polysomnography, represents a useful and cost-effective tool to assess pediatric insomnia and response to treatment. It is based on small wristwatch-like devices that monitor movements for extended periods of time. The raw activity scores (i.e., epochs) are translated to sleep/wake scores based on computerized scoring algorithms. There are different commercial devices in the market, and each device has its own measurement characteristics [59].

Actigraphy can be placed on the nondominant wrist, but may also be placed on the dominant wrist, the ankles, or the trunk; extended monitoring (5 days or longer) reduces the inherent measurement errors in actigraphy and increases reliability.

Sleep parameters most closely estimated by actigraphy include sleep duration, sleep efficiency, and waking time after initial sleep onset. A concomitantly maintained sleep log provides important supplemental data for accurate interpretation of actigraphy. Actigraphy-documented improvement in sleep may constitute a strong positive feedback for parents to constantly implement and apply behavioral strategies.

Finally, in adolescence it could be important also to evaluate the body clock type of the patient to exclude circadian rhythm disorders: (a) Morning chronotypes, also referred to as larks or early risers, prefer relatively early bed and wake-up times, and they describe their optimal mental and physical performance to be in the early part of the wake episode; (b) evening chronotypes, sometimes referred to as owls or late sleepers, prefer relatively late bed and wake-up times, and they describe their period of optimal mental and physical performance to be late in the wake episode. The hallmark of circadian rhythm disorders is that when the child is allowed to sleep at his or her desired schedule, sleep is normal and daytime sleepiness rapidly subsides.

Hypothesis on a Clinical Classification of Pediatric Insomnia

Although several studies have been published on the treatment of insomnia in infants and children, the translation of research findings to practice settings remains unclear for several reasons:

  1. (a)

    Most treatment studies define sleep problems by symptoms and fail to classify using diagnostic criteria [60, 61].

  2. (b)

    There is no indication on the appropriate treatment for specific insomnia subtypes [62].

  3. (c)

    There is no clear evidence on frequency and duration of non-pharmacological and pharmacological treatment [41].

  4. (d)

    There are no long-term follow-up studies either for non-pharmacological and pharmacological treatment.

  5. (e)

    No specific instruments for assessing the severity of insomnia are available.

The generic classification insomnia in ICSD-3 and DSM-V incorporating adult and pediatric insomnia into a unique entity might be misleading for clinicians and might be difficult to define the exact type of insomnia and to find the correct patient-oriented treatment approach, either non-pharmacological or pharmacological.

In order to guide the decision on the best treatment approach of pediatric insomnia, we hypothesize a clinical categorization of childhood insomnia that might be conceptualized as follows [63–65]:

  • Insomnia with motor hyperactivity

  • Insomnia with prevalent middle-of-the-night awakenings

  • Insomnia with multiple night awakenings and falling asleep difficulties

These three different types are the most commonly encountered in the pediatric sleep field and can be easily identified in the clinical practice. They might be related to different pathophysiological mechanisms:

  1. (a)

    The insomnia characterized by motor hyperactivity (parental report of a child that kicks the legs or described as a “horse in the bed”) is probably linked to a dopaminergic dysfunction since it could represent the early manifestations of the restless legs syndrome reported by Picchietti et al. [66]. In a recent study, it has been shown that symptoms of restless legs syndrome may already start in the first year of life and are related to low serum ferritin level. The authors showed that the most striking single symptom was awakening after 1–3 h of sleep followed by screaming, crying, kicking, and slapping the legs or by verbally expressing that the legs “hurt” with a seemingly comforting effect of massage and cycling movements performed by the parents [67]. Recently, we described the case of a toddler with severe insomnia, bedtime and nocturnal hyperactivity, and night awakenings associated with leg kicking and rubbing, highly suggestive of restless legs syndrome but presenting as severe insomnia responsive to gabapentin [64, 65].

  2. (b)

    The insomnia with prevalent middle-of-the-night awakenings could resemble the insomnia of people with mood disorders, that is, mainly characterized by no falling asleep troubles but prolonged midnight awakening with difficulty returning to sleep. Recent studies have demonstrated a link between sleep difficulties in childhood and depression in mid-adolescence [68] and in adulthood [69] and an improvement of sleep quality with the administration of some antidepressants: 5HT2A receptor antagonists determined an increase of slow-wave sleep, a reduction of REM, and an improvement of sleep continuity [70].

  3. (c)

    The insomnia with multiple night awakenings and falling asleep difficulties is often a symptom related to infants who present with milk allergy or gastroesophageal reflux and therefore are highly suspected to be related to a histaminergic dysfunction. The histaminergic system in the brain is exclusively localized within the posterior hypothalamus with projection to almost all the major regions of the central nervous system. Administration of histamine or H1 receptor agonists induces wakefulness, whereas administration of H1 receptor antagonists promotes sleep. The first generation of antihistamines easily penetrates the blood-brain barrier and causes drowsiness and sedation. Several of these antihistamines, including the nonselective H1 receptor antagonists from the phenothiazine class and “over the counter” diphenhydramine, have positive effects on subjective and objective measures of nocturnal sleep in healthy human subjects [71].

This kind of categorization has important implications for treatment and could allow the clinicians to personalize pharmacological therapy, based on the hypothesized neurotransmitter dysfunction.

This approach is also based on the results of recent genetic studies suggesting that genetic factors play an important role on the development of insomnia of childhood. For example, heritability contributed for 30.8 % on nocturnal sleep duration, for 36.3 % on diurnal sleep duration, and for 35.3 % on night wakings [72]. Furthermore, the variance in consolidated nighttime sleep duration is largely influenced by genetic factors with a critical environmental time-window influence at around 18 months. A strong heritability (71 %) was observed for the short-persistent nighttime sleep duration trajectory [73].

In order to correctly categorize the specific type of insomnia, a careful family and personal history should be collected to evaluate the presence of symptoms/diseases that could be associated with the hypothesized classification of insomnia. LeBlanc et al. [74] point out that family history was the second strongest predictive factor in new cases of insomnia syndrome with the implication that there may be a familial predisposition and, in other words, a vulnerable phenotype. Further, there was a trend toward a higher familial incidence in those reporting earlier onset vs. those reporting a later onset. Furthermore, evidence suggests that the expression of 5HTTLPR, which affects synaptic serotonin levels, is critical in the development of the neonatal brain, and also the 5HTTLPR contributes to the onset of insomnia rather than the severity [75].

However, also several epigenetic mechanisms seem to be involved in the regulation of sleep and in the development of insomnia: stressful experiences during prenatal/early life development may contribute to changes in stress reactivity that may persist into adulthood through epigenetic mechanisms. If epigenetic mechanisms are potentially reversible via environmental or pharmacological interventions, it might be hypothesized that both cognitive behavioral treatment for insomnia and pharmacological interventions might influence epigenetic modification in insomnia [76].

From the previous studies, it is clear that a predisposition to insomnia seems to exist, driven by factors associated with response to stress at both a psychological and physiological level. Understanding vulnerability to insomnia will inform our understanding of the etiology of other disorders, specifically depression.

To summarize our hypothesis on the different types of insomnia reported above, we propose the following treatment approach:

  1. (a)

    An infant who presents with no particular difficulties in falling asleep but prolonged middle-of-the-night awakenings and a family and clinical history of insomnia, parasomnias, headache/migraine, depression, and mood disorders probably underlies a serotonergic dysfunction and therefore should be treated with serotonergic drugs. Obviously selective serotonin reuptake inhibitors (SSRI) are not indicated in infants and children, and therefore L-5-hydroxytryptophan could be the choice for this type of insomnia.

  2. (b)

    An infant presenting with difficulty in falling asleep linked to restless legs or kicking legs and with nocturnal hyperactivity and a family and clinical history of restless legs syndrome or periodic limb movements during sleep, iron deficiency anemia, and growing pains might indicate a dopaminergic dysfunction and should be evaluated for anemia and eventually treated with iron.

  3. (c)

    An infant showing multiple night awakenings and falling asleep difficulties with a clinical history of atopic dermatitis or milk allergy or gastroesophageal reflux and with a high presence of allergies in the family might reveal a histaminergic dysfunction. In this case obviously the treatment of choice should be the first generation of antihistamines with high affinity for the H1 receptor.

Treatment of Pediatric Insomnia

Prevention is the best treatment for behavioral insomnia of childhood, but unfortunately, most frequently parents request an evaluation when the disorder is chronic. Good sleep practices and behavioral interventions are the first recommended treatments for pediatric insomnia [27]. It is important to discuss parents’ knowledge and beliefs as well as strategies they have used to help address their child’s sleep problems. For example, in the case of multiple night awakenings, it assumes crucial importance to clarify age-appropriate sleep structure: although parents often perceive that their children with night wakings have more frequent arousals than do other children, arousals are a normal part of sleep architecture and are experienced equally by children with and without reported night waking. It is the child’s signaling at times of waking – by crying, calling, or getting out of bed (because of difficulty returning to sleep independently) – that makes the parents aware of, and thus report as frequent, the night wakings [77].

Sleep Hygiene

Sleep hygiene plays an important role in virtually all sleep interventions and typically involves a combination of creating an environment that is conducive to sleep and engaging in healthy sleep habits. In terms of environment, the bedroom should be quiet and dark and have a cool temperature [78].

Scheduling regular, appropriate sleep and wake times allows an adequate sleep opportunity. In addition, the bedroom should be envisioned as a calming, relaxing sleep sanctuary. For this reason, televisions, video games, and other electronic devices should not be kept in the bedroom, and parents should not use the bedroom as a place to send the child when they are punished [79, 80].

The above strategies will work best when used in combination with healthy sleep hygiene habits. These include implementing a regular bedtime routine (e.g., bathe, get in pajamas, brush teeth, read a book, say goodnight) and a consistent sleep schedule, avoiding stimulating activities (e.g., watching television or playing video games) prior to bedtime, limiting caffeine (e.g., cola and chocolate) intake before bed, and engaging in daily physical activity [81].

As with infants and toddlers, parents play a crucial role in treating sleep problems in this age group. It is important that parents model and begin to teach their preschoolers about healthy sleep hygiene. With their parents’ help, preschoolers can begin to play a more active role in choosing appropriate sleep hygiene options (e.g., choosing to read a book rather than watch television right before going to sleep). The earlier sleep hygiene habits are established, the better, as sleep habits developed in childhood shape sleep habits exhibited in adulthood.

Addressing nighttime fears in this age group can help reduce negative associations with sleep and may be another important aspect of intervention that should be considered. A common intervention for nighttime fears in children is for the parent to make the child feel safe and secure by co-sleeping (e.g., allowing the child to sleep in the parent’s bed). Although this intervention offers short-term alleviation of symptoms, parents often find themselves co-sleeping for extended periods of time. This habit can be challenging to change and often results in the need for an intervention for co-sleeping.

Healthy sleep practices include daytime and nighttime sleep practices that positively impact sleep initiation/maintenance and sleep quantity and quality; it usually includes bedtime routine, consistent bedtime and wake time, a quiet, dark, and cool bedroom, avoidance of caffeinated products, and daily physical activity (Table 9.1). A critical aspect of sleep hygiene is the use of technology in the bedroom (computer, TV, cell phone, video games), which is clearly associated with decreased sleep quantity and quality in children [82].

Table 9.1 Healthy sleep practices
Full size table

Non-pharmacological Treatment

Behavioral treatment for bedtime problems and night wakings is claimed to be highly effective in improving child sleep [27]; no published studies have shown any adverse effects of behavioral interventions for bedtime problems and night waking in young children, including interventions involving periods of crying in infants and toddlers [83, 84].

The American Academy of Sleep Medicine published recommendations for behavioral treatment of bedtime problems and night awakenings in infants and young children [60–62]; cardinal elements of a behavioral treatment plan for infant and young children are optimization of sleep hygiene, maintaining a regular sleep schedule, and structured bedtime routines appropriate for age, such as bathing, toothbrushing, or reading stories. Exposure to ambient light at bedtime and during the night should be minimized except for small night lights in cases of children with fear of the dark.

Recent studies showed parent education to be efficacious [85].

For more specific behavioral interventions, there is no evidence to suggest any one approach is more effective than another. Thus parents should be presented with different options and select an approach that matches the infant’s temperament and family’s preferences. With any strategy, it is important to problem solve with parents how to handle child distress (e.g., parent engages in a distracting activity during infant crying or contact with another supportive adult during the process). With all behavioral interventions, it is important to explain to parents that although the first night will be challenging, the second night will be worse, and that the parents must persist and remain consistent [27].

Treatment of insomnia for older children and adolescents is seldom successful unless all pertinent influences are addressed and the child is motivated enough to make the lifestyle and sleep schedule changes that are usually necessary to correct the problem [13]; consumption of caffeinated beverages should be reduced and any late-day intake should be eliminated. The use of electronic devices should be moved to alternative times and optimally replaced with a structured pre-bedtime routine incorporating less stimulating activities. Efforts should be made to keep bedtime and waking time on non-school days consistent with those on school days to eliminate irregularity of sleep schedule. Daytime napping should be eliminated.

Several behavioral techniques are available, and the clinician should propose to the family the most appropriate, based on parental preferences and child temperament [86]; consistent and sustained application of these interventions is usually necessary to achieve sustained clinical improvement in children with more severe forms of bedtime resistance and night waking.

Positive Routines

Positive routines involve the parents developing a set bedtime routine characterized by quiet activities that the child enjoys. Faded bedtime with response cost involves taking the child out of bed for prescribed periods of time when the child does not fall asleep. Bedtime is also delayed to ensure rapid sleep initiation and that appropriate cues for sleep onset are paired with positive parent-child interactions. Once the behavioral chain is well established and the child is falling asleep quickly, the bedtime is moved earlier by 15–30 min over successive nights until a preestablished bedtime goal is achieved.

Unmodified Extinction

Extinction has been found to be an effective intervention for sleep problems in infants and very young children [87].

In fact, most behavioral methods for treating sleep problems in these age groups incorporate principles of extinction. Extinction is based on the hypothesis that night wakings and attention-seeking behaviors are positively reinforced by parental attention and other behaviors. Thus, extinction involves parents helping their children to establish self-soothing skills (e.g., parents are told to put their infants to bed drowsy, but not asleep, which helps the child learn to settle to sleep on his/her own). The parent is not to respond to their child’s attempts at reengaging the parent to provide external soothing techniques (e.g., feeding, rocking, singing). The goal is for the child to learn to self-soothe.

The biggest obstacle associated with extinction is lack of parental consistency. Parents must ignore their child’s cries every night, no matter how long it lasts. Many parents are unable to ignore crying long enough for the procedure to be effective.

Tikotzky and Sadeh [87] reported that it can be helpful and encouraging to inform parents that research has not found that limiting parental involvement in order to promote self-soothing results in adverse effects on the infant’s emotional well-being or on the parent-child relationship. The child is placed in bed while awake, left alone until asleep, and night wakings are ignored. The infant learns to self-soothe once realizing that nighttime crying does not result in parental attention.

If parents respond after a certain amount of time, the child will only learn to cry longer the next time. Parents are also instructed that post-extinction response bursts may occur. That is, often at some later date, there is a return of the original problematic behavior. Parents are instructed to avoid inadvertently reinforcing this inappropriate behavior following such an extinction burst. The common term used in the media and self-help books to describe unmodified extinction techniques is the “cry it out” approach.

As a variant to unmodified extinction, some studies have utilized extinction with parental presence. (The parent remains in the room during extinction, acting as a reassurance for the child but providing little interaction.) This procedure involves the parents staying in the child’s room at bedtime but ignoring the child and his/her behavior. Some parents find this approach more acceptable and are able to be more consistent.

Graduated Extinction

For parents who are opposed to unmodified extinction, other variants of extinction, such as graduated extinction or parental presence extinction, may be a better intervention alternative. Graduated extinction involves parents ignoring disruptive bedtime behaviors for a predetermined period. If the child has not settled at the end of that time, the parent settles the child back in bed, but minimizes interaction with the child. Extinction with parental presence involves the parent lying down in a separate bed in the infant’s room during settling and awakening. Parents feign sleep and do not attend to the infant directly. Parents follow this procedure for 1 week, after which they follow an unmodified extinction procedure. This technique has been found to reduce the extinction burst (increase in signaling behaviors) that is typically seen when using unmodified extinction. This involves ignoring negative behaviors (i.e., crying) for a given amount of time before checking on the child. The parent gradually increases the amount of time between crying and parental response. Parents provide reassurance through their presence for short durations and with minimal interaction.

Either parents can employ a fixed schedule (e.g., every 5 min), or they can wait progressively longer intervals (e.g., 5 min, 10 min, then 15 min) before checking on their child. With incremental graduated extinction, the intervals increase across successive checks within the same night or across successive nights. The checking procedure itself involves the parents comforting their child for a brief period, usually 15 s to a minute. The parents are instructed to minimize interactions during check-ins that may reinforce their child’s attention-seeking behavior.

The goal of graduated extinction is to enable a child to develop “self-soothing” skills in order for the child to fall asleep independently without undesirable sleep associations (e.g., nursing, drinking from a bottle, rocking by parent). Once these skills are established, the child should be able to independently fall asleep at bedtime and return to sleep following normal nighttime arousals.

Scheduled Awakenings

Scheduled awakening entails establishing a baseline of the number and timing of spontaneous night wakings. Then a preemptive waking schedule wherein parents awaken their child approximately 15–30 min before typical spontaneous night waking is implemented. As the treatment progresses, the time between scheduled awakenings is increased until eventually there are no awakenings. When parents awaken the child, they are instructed to engage in their typical behaviors (e.g., feeding, rocking, soothing) as if the child had awakened spontaneously.

Scheduled awakenings appear to increase the duration of consolidated sleep, but the mechanisms behind why this intervention decreases nighttime awakenings are not well understood. Scheduled awakenings are a treatment option for frequent nighttime awakenings, but are not appropriate for problems with sleep initiation. Also, compared to extinction, it can be more complicated to carry out and may take several weeks rather than days before improvements are seen.

Bedtime Fading

Faded bedtime, often used in combination with sleep hygiene, involves determining a time at which it is likely the child will fall asleep within about 15 min of going to bed [88].

Once the child falls asleep at this time with little resistance, the bedtime is set earlier after a series of successful nights until the desired bedtime is achieved. Also, the child’s wake time is set at the same time each day, and the child is not allowed to sleep outside the prescribed sleep times. A modified version of this technique, faded bedtime with response cost, involves bedtime fading, as described above. However, if the child does not fall asleep within a certain period of time, the child is removed from bed (response cost) to decrease the negative association between being in bed and awake and to increase the likelihood that the child will fall asleep. After a predetermined time (typically about 30 min during which time the child engages in a non-arousing activity), the child returns to bed. This procedure is repeated until the child falls asleep. Once successful at the target bedtime, an earlier bedtime is set as the goal. The aims of the treatment are in line with the goals of extinction: to increase appropriate behaviors and positive associations with sleep and to decrease arousal by helping the child to develop self-soothing skills and fall asleep independently. This technique involves delaying bedtime closer to the child’s target bedtime. The goal of this treatment is for the child to develop a positive association between being in bed and falling asleep rapidly. Bedtimes can be gradually moved earlier.

Efficacy Studies on Behavioral Treatments

It should be taken into account that the long-term efficacy of behavioral treatment is not completely assessed: a systematic review, although acknowledging the efficacy in short term, reported finally that moderate-level evidence supports behavioral interventions for pediatric insomnia in young children and even low evidence in adolescents and in children with neurodevelopmental disabilities. This review showed that only four studies assessed sleep-onset latency, with a significant overall effect and small to medium effect size at posttreatment. Also the evaluation of the efficacy on the frequency of night wakings (seven studies), and on the night waking duration (four studies), resulted in a significant effect but with a small to medium effect size. Finally, a nonsignificant overall effect on night wakings was found at 3–12-month follow-up across five studies [89].

Following the results of this study, we should reconsider the claimed “efficacy” of behavioral interventions; more studies are needed to identify factors that may predict treatment success and to tailor behavioral interventions for young children based on child (e.g., temperament, age), parental, and environmental factors [86]. Finally, more longitudinal studies are needed to demonstrate whether treatment benefits for insomnia are maintained over time and to examine other functional outcomes (child mood, behavior, health, as well as parental mood, marital satisfaction, and family functioning).

Box: Behavioral Strategies for Insomnia of Childhood

  1. 1.

    Create solid and positive bedtime routines (e.g., songs, books, relaxing activities).

  2. 2.

    If possible, put the child in bed sleepy but not fully asleep.

  3. 3.

    Put in the child’s bed only few familial objects he can use to sooth himself in the case of nocturnal awakenings (avoid plushes or dangerous objects).

  4. 4.

    Establish a constant “good-bye phrase,” for example, “You can sleep alone here with your favorite toys.”

  5. 5.

    Before leaving the child’s room, give a plausible explanation (“mama will go to the kitchen to drink some water and then come back to you”).

  6. 6.

    Speak to the child from the other room to reassure him.

  7. 7.

    If he begins to cry, let him cry for a brief period (5–10 s) before returning in the room.

  8. 8.

    Reassure the child, letting him in his bed and remain in the room until he has calmed down; reduce as much as possible the direct interaction with the child.

  9. 9.

    Leave the room repeating point 4.

  10. 10.

    If the child cries, return in the room and repeat point 7 awaiting a little more time (10–15 s).

  11. 11.

    Next night, repeat from point 1 to 10, increasing time of awaiting of 10 s.

For waiting times in case of nocturnal awakenings, follow those indications:

 

1° awakening (s)

2° awakening (s)

3° awakening (s)

Day 1

10

15

20

Day 2

20

25

30

Day 3

30

35

40

Day 4

40

45

50

Day 5

50

55

60

Day 6

60

65

70

Day 7

70

75

80

Pharmacological Treatment

Children who do not respond to behavioral interventions could be candidates for pharmacological treatment of insomnia. Currently, there are no US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia in children, and pharmacological treatment should always be considered in combination with behavioral treatment [26, 90].

Due to the lack of studies and of empirical evidence, different drugs have been traditionally used in pediatric insomnia and especially in children with special needs. Most used medications are sedating antihistamines (e.g., diphenhydramine and hydroxyzine), melatonin, benzodiazepines, α-2-receptor agonists (e.g., clonidine), pyrimidine derivatives (e.g., zaleplon and zolpidem), antipsychotics (e.g., risperidone and quetiapine), and sedating antidepressants (e.g., trazodone and mirtazapine) [90].

Clear, well-defined treatment goals must be established with the patient and family. Treatment goals should be realistic, clearly defined, and measurable, for example, it has to be clarified that the immediate goal of treatment will usually be to alleviate or improve, rather than to completely eliminate, sleep problems. Close communication with the family, including during frequent follow-up visits, is a key component of successful and safe management.

It should be taken into account that drugs could be initially useful for parent and child’s relief, and in general it is better not to wait a long time to treat insomnia; it is better to implement a brief drug trial than act later on a chronic insomnia. Also when a drug has been administered, abrupt discontinuation should be avoided, and the treatment should be carefully monitored since there is a natural inclination of the parents to give the lowest dose [91]. Finally, it should be reminded that cognitive behavioral therapy should always be associated to drug treatment to ensure the best long-term efficacy [41].

It is of interest that about 50–60 % of pediatricians use drugs for insomnia in infants and children [92–95], but despite the widespread use of prescription therapies such as clonidine, antidepressants, mood stabilizers, and antihistamines, little data exist on their efficacy for the treatment of insomnia in children and adolescents [60, 61]. Few studies have evaluated pharmacologic interventions for childhood insomnia refractory to behavioral interventions, and even fewer have included children with neurodevelopmental or neuropsychiatric disorders.

Commonly, parents who ask for consultation for insomnia of the infant/child have already tried homeopathic, non-prescription, and off-label prescription agents, because of safety, economy, and evidence.

In the following paragraphs, different homeopathic, off-label prescription agents and drugs commonly used for insomnia are listed.

Tryptophan

Tryptophan is a precursor of serotonin and melatonin widely used in the 1980s for treatment of sleep disorders and headache prophylaxis. It does not have opioid-like effects and does not limit cognitive performance or inhibit arousal from sleep [96]. In the literature, several positive effects on sleep are reported: improvement of sleep latency [97–99].

The exact mechanism of action of the sedative effects of L-tryptophan is unknown, but the effect is not mediated by the conversion in serotonin.

5-Hydroxytryptophan (5-HTP)

5-HTP is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. 5-HTP is not found in the foods and eating foods with tryptophan slightly increases 5-HTP levels. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. The effects of 5-HTP on sleep structure are conflicting: increase or decrease of REM and increase of SWS [100].

In 1989, the presence of a contaminant called Peak X was found in tryptophan supplements that could determine eosinophilia-myalgia syndrome (EMS); however, a recent study reported that there is no evidence to implement 5-HTP intake as a cause of any illness, especially the EMS or its related disorders [101].

Very limited data are available on the effects of 5-HTP on insomnia symptoms.

There is clear evidence of therapeutical effect for sleep terrors in children at dosage of 2 mg/kg [92, 93].

Antihistamines

Histamine is a wake-promoting neurotransmitter, and inactivation or suppression in various animal models has led to sedation and disrupted wakefulness patterns [102].

The first generations of antihistamines are lipid soluble and pass through the blood-brain barrier; they bind to H1 receptors in the CNS and have minimal effects on sleep architecture. They are often the more acceptable choice for many families, commonly well tolerated, and may acutely improve sleep and speed up behavioral programs.

These agents may worsen obstructive sleep apnea (OSA), and also may suppress rapid eye movement (REM) sleep [90].

Diphenhydramine is the most commonly used and is a competitive H1-histamine receptor blocker. Peak blood and tissue levels are achieved within 2 h of ingestion. The recommended dosage for adults is 25–50 mg, whereas in children the effective dose is between 0.5 mg/kg and 25 mg. A study showed a significant decrease in sleep latency time and number of awakenings [103], while other studies reported no more effectiveness than placebo [104, 105].

Very few studies have been conducted with other antihistamines in children with insomnia, reporting conflicting results. Trimeprazine was used in 22 children with night wakings showing a moderate improvement [106]; niaprazine showed a decrease of sleep-onset latency and an increase of sleep duration [107] even if compared with benzodiazepines [108].

The most common adverse reaction to antihistamines at therapeutic doses is impaired consciousness. The predominant features in an overdose are anticholinergic effects, including fever, blurred vision, dry mouth, constipation, urinary retention, tachycardia, dystonia, and confusion.

Melatonin

Melatonin (N-acetyl-5-methoxytryptamine) is a chronobiotic drug crucial for the regulation of the sleep/wake cycle. In older children and adults, its production and secretion begin in the evening and peak during the night between 2:00 and 4:00 AM; its production and release are inhibited by light. There is now a greater understanding that low doses (0.5 mg) can be effective for some children, with diminishing benefit with doses exceeding 6 mg, and unlike traditional hypnotics such as chloral hydrate and the benzodiazepines, melatonin does not affect sleep architecture [24].

In general MLT for treatment of chronic sleep-onset insomnia in children is effective in a dosage of 0.05 mg/kg given at least 1–2 h before desired bedtime [109].

Systematic reviews and meta-analyses of placebo-controlled, randomized controlled trials (RCTs) in children with neurodevelopmental disabilities, especially autism, have demonstrated that exogenous melatonin improves sleep, either by reducing the time taken to fall asleep (sleep-onset latency) or by increasing total sleep time (sleep maintenance and sleep efficiency), or both [110, 111].

Further, MLT at a dosage of 5 mg was effective in ADHD children with delayed sleep-phase syndrome (DSPS) and insomnia [112–115].

These effects have been also observed in typically developing children with delayed sleep-phase syndrome.

Melatonin is increasingly prescribed to many children using a wide range of doses, demonstrating efficacy in improving sleep quality, by reducing sleep-onset latency or slightly increasing total sleep time.

A large clinical trial confirmed the efficacy of melatonin in the treatment of sleep impairment in children with NDDs, using different doses, ranging from 0.5 to 12 mg; the main effects of melatonin were reduced sleep latency (from 102 to 55 min in 12 weeks) and increased total sleep time (40 min) [116].

Headaches, confusion, dizziness, cough, and rashes have been reported, but these are common symptoms in children and are likely to be coincidental or caused by impurities in the many imported and often unregulated formulations of melatonin. Previous reports of poor seizure control, poor asthma control, and adverse endocrinological problems during puberty have not been confirmed. The systematic reviews and meta-analyses of RCTs all suggest that there are no significant adverse side effects associated with the use of melatonin [24].

Further research is required to evaluate the metabolism of melatonin, the function of its receptors, and its value in specific neurodevelopmental disorders. Unanswered clinical questions include whether slow-release preparations are superior to immediate-release in increasing total sleep time, and whether a more rational and optimal prescription of melatonin might be achieved by measuring salivary melatonin before its use.

Iron

Iron is a cofactor for tyrosine hydroxylase, the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dopamine.

Iron deficiency anemia was reported to be associated with higher motor activity during sleep, shorter night sleep duration, and higher frequency of night waking [117], and supplemental iron was associated with longer sleep duration [118].

In some cases, night awakenings starting in the first year of life might be an early sign of restless legs syndrome [119, 120].

This kind of insomnia with motor hyperactivity and characterized by awakening after 1–3 h of sleep followed by screaming, crying, kicking, and slapping the legs or by verbally expressing that the legs “hurt” with a seemingly comforting effect of massage and cycling movements performed by the parents is reported to be related to low serum ferritin level [67].

Because iron deficiency is common in children, measuring the ferritin level is reasonable. Iron replacement should be initiated if ferritin levels are less than 50 mcg per L, and they should be rechecked in 3 months [121]; although the risk of iron overload is very low, parents should be asked for a personal and family history of hemochromatosis or unexplained liver disease.

Vitamin D

Clinical research on the relation between vitamin D and sleep is ongoing, and few studies have been published on the role of vitamin D metabolism and sleep disorders. Preliminary data suggest the possibility that altered vitamin D metabolism could play an important role in the presentation and severity of sleep disorders [122]. Vitamin D is related to dopamine metabolism; it could be useful to investigate vitamin levels in association with iron parameters in children with motor hyperactivity during sleep.

Clonidine

Clonidine is a central α2 agonist that has been widely used in treating sleep disturbances (mainly sleep-onset delay) in children with ADHD [123].

Clonidine is rapidly absorbed and has onset of action within 1 h and peak effects in 2–4 h. Starting dose is usually 50 μg, increased in 50 μg increments.

Tolerance to the sedating effects may develop with sedative effects tending to decrease over time, thus necessitating gradual increases in dose and associated increased potential for adverse effects.

No randomized trials of clonidine specifically for children with insomnia exist, but the few studies showed a certain efficacy on sleep latency and night wakings. Side effects include hypotension, bradycardia, irritability, anticholinergic effects (e.g., dry mouth), and REM suppression [124].

Clonazepam

Benzodiazepines bind to the benzodiazepine subunit of the gamma aminobutyric acid (GABA) chloride receptor complex, facilitating the action of the inhibitory neurotransmitter GABA. These hypnotics have long been the first-choice treatment for insomnia in adults, but raise concerns about cognitive impairment, rebound insomnia, and the potential risk for dependence. These concerns, and little evidence-based data availability in the pediatric population, contribute to limit their use in children [125]. Possible side effects include daytime sedation, hypotonia, rebound insomnia on discontinuation, psychomotor/cognitive impairment, and impairment of respiratory function [126].

Zolpidem

It is a non-benzodiazepine receptor agonist (NBzRA) that binds preferentially to GABAA receptor complexes containing α1 subunits; it has minimal effects on sleep architecture with a slight increase to slow-wave sleep [127].

There are very few studies conducted in children. A study on 6–11 years or 12–17 years children with ADHD and insomnia received treatment with zolpidem at 0.25 mg/kg per day (max 10 mg/day) vs. placebo. Mean change in latency to persistent sleep at week 4 did not differ between zolpidem and placebo groups. No next-day residual effects of treatment and no rebound phenomena occurred after treatment discontinuation. Most-frequent adverse events (>5 %) were dizziness, headache, and hallucinations [128]; also disinhibition and hallucinations have been reported [129]..

Mirtazapine

Mirtazapine is an α2-adrenergic, 5-HT receptor agonist with a high degree of sedation at low doses; this may result in residual daytime sleepiness [130]. It has been shown to decrease sleep-onset latency, increase sleep duration, and reduce wake after sleep onset (WASO), with relatively little effect on REM [131].

Trazodone

Trazodone is one of the most sedating antidepressants and the most widely studied of antidepressants in terms of sleep. It is a 5-HT2A/C antagonist and inhibits postsynaptic binding of serotonin and blocks histamine receptors. Trazodone suppresses REM sleep and increases slow-wave sleep; side effects are represented by morning hangover (common), hypotension, arrhythmias, and serotonin syndrome [132].

A resume of dosage, side effects, and indications is reported in Table 9.2.

Table 9.2 Selected medications for the treatment of insomnia
Full size table

Conclusions

Insomnia in children has multifactorial origin and can cause impairment in quality of life of both patients and families.

The medical approach should follow the pathway of sleep medicine, examining medical and genetic contributing factors to find a patient-oriented treatment approach. Behavioral treatment strategies and pharmacological options are available. Despite the widespread use of pharmacological treatment, the lack of well-designed, controlled studies concerning the efficacy, tolerability, dosage, and safety profile of hypnotic medications in children raise the need of further research in this field of sleep medicine.