Separation anxiety disorder ICD code F93.0 occurs in youth younger than 18 years (persistent and lasting for at least 4 weeks) and in adults (typically requiring a duration of 6 mo or more). Separation anxiety disorder can also be associated with panic attacks that can occur with comorbid panic disorder. Separation anxiety disorder consists of persistent and excessive anxiety beyond that expected for the child's developmental level related to separation or impending separation from the attachment figure (eg, primary caretaker, close family member) as evidenced by at least 3 of the following criteria from the DSM-5:
In order to meet criteria for this disorder, it must cause clinically significant distress or impairment in social, academic, occupational, or other important areas of functioning and is not better explained by another mental disorder such as refusing to leave home because of excessive reluctance to change in autism spectrum disorder, delusions or hallucinations concerning separation in psychotic disorders, refusal to go outside without a trusted companion in agoraphobia, worries about ill health or other harm befalling significant others in generalized anxiety disorder, or concerns about having an illness in illness anxiety disorder.[1]
Separation anxiety is often the precursor to school refusal, which occurs in approximately three fourths of children who present with separation anxiety disorder. It is important to screen for selective mutism because some children may have school refusal as a symptom of selective mutism. The diagnosis of selective mutism involves a comprehensive evaluation, including ruling in or out comorbid conditions such as expressive and receptive language delays and other communication disorders.[2, 3]
Panic attacks are commonly associated with separation anxiety disorder both in youths and adults.[4, 5]
Panic attacks can also be a cause of school refusal.[6]
According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), separation anxiety disorder (code 309.21/F93.0) is a fairly common anxiety disorder, occurring in youth younger than 18 years (persistent and lasting for at least 4 weeks) and in adults (typically requiring a duration of 6 mo or more). Separation anxiety disorder can also be associated with panic attacks that can occur with comorbid panic disorder. Separation anxiety disorder consists of persistent and excessive anxiety beyond that expected for the child's developmental level related to separation or impending separation from the attachment figure (eg, primary caretaker, close family member) as evidenced by at least 3 of the following criteria:
In order to meet criteria for this disorder, it must cause clinically significant distress or impairment in social, academic, occupational, or other important areas of functioning and is not better explained by another mental disorder such as refusing to leave home because of excessive reluctance to change in autism spectrum disorder, delusions or hallucinations concerning separation in psychotic disorders, refusal to go outside without a trusted companion in agoraphobia, worries about ill health or other harm befalling significant others in generalized anxiety disorder, or concerns about having an illness in illness anxiety disorder. (See Epidemiology, History.)[1]
Separation anxiety is often the precursor to school refusal, which occurs in approximately three fourths of children who present with separation anxiety disorder. It is important to screen for selective mutism because some children may have school refusal as a symptom of selective mutism. The diagnosis of selective mutism involves a comprehensive evaluation, including ruling in or out comorbid conditions such as expressive and receptive language delays and other communication disorders.[2, 3] Also see Anxiety Disorders, Social Phobia and Selective Mutism. (See Epidemiology.)
Panic attacks are commonly associated with separation anxiety disorder both in youths and adults.[4, 5]
Panic attacks can also be a cause of school refusal.[6]
Separation anxiety is developmentally normal in infants and toddlers until approximately age 3-4 years, when mild distress and clinging behavior occur when children are separated from their primary caregivers or attachment figures (eg, being left in a daycare setting).
Separation anxiety disorder generally manifests with clinically significant symptoms of anxiety, such as unrealistic and recurrent worries about harm occurring to loved ones, especially when separated or faced with threatened separation from the primary attachment figure, along with severe distress and impairment in functioning. The DSM-5 includes criteria for adult separation anxiety disorder that do not require a childhood history of the disorder, although this finding is common.[4, 5] (See History.) Severe distress and impairment in functioning may be indicated by the following signs:
Boys and girls do not significantly differ in symptom presentation.
In addition, physical/somatic symptoms (especially frequent in older children and adolescents), such as dizziness, lightheadedness, nausea, stomachache, cramps, vomiting, muscle aches, or palpitations, may be present and problematic, causing the child and family to seek medical treatment because of impaired ability to attend school or meet social responsibilities. (See Epidemiology, History.)
Transient developmental fears (eg, fear of the dark) are generally normal and do not interfere with normal functioning or result in long-term developmental difficulty; however, studies show a subgroup of children who do not meet the criteria for diagnosis of an anxiety disorder but who may have substantial impairment later in life.
Studies of children who, in first grade, present with significant symptoms of anxiety (enough to cause clinically significant impairment in social and academic functioning) reflect a correlation with significant impairment in reading and math achievement 5-6 years later.
Complications of separation anxiety can also include the following:
Long-term follow-up studies of children successfully treated for school refusal because of separation anxiety reveal that some children have continued impairment of social functioning (ie, social and affective constriction), despite having returned to school. This may reflect the long-term impairment and morbidity and unchanging dysfunctional parent-child interaction at home. (See Treatment and Management.
A recent study found that for cognitive-behavioral therapy (CBT), the quality of the treatment relationship between the youth and the therapist plays a significant role in outcome. A very strong treatment relationship predicted positive outcome with CBT alone; for youths treated with sertraline alone or combination treatment with sertraline and CBT, there appeared to be less influence on outcome related to the quality of the treatment relationship, with a possible implication that externally imposed biochemical influences on brain functioning might be able to override relationship-based influences on anxiety.[7]
Prompt treatment of school refusal is key to shorten the course of the disorder, as is it challenging to reduce the tangible reinforcement of school nonattendance. Without treatment, as many as 40-50% of these youths are at risk for not graduating high school due to the intensity and chronicity of their anxiety.[8]
A study of 62 school-refusing adolescents (ages 11 to 16.5 years) using a randomized controlled trial design in Australia found more improvement in anxiety and depressive symptoms than in school attendance, underscoring the long-term nature of school refusal, thus a chronic care approach to school refusal is needed even through combined treatment – augmentation of cognitive behavior therapy (CBT) with fluoxetine improved outcomes.[9]
Basic science studies of rhesus macaques have shown that an early history of exposure to traumatic events may alter infant caregiver bonding by causing altered functioning of the oxytocin receptor; this may have implications for treatment approaches.[10]
An article published in February 2017 in the Journal of the American Academy of Child and Adolescent Psychiatry by Rogers, Sylvester, Mintz, Kenley, Shimony, and Barch shed a light on a possible underlying neuroanatomical mechanism for separation anxiety.[11]
Rogers et al. found that variability of regional neonatal amygdala resting state functional connectivity predicted internalizing symptoms at 2 years of age, suggesting that risk for internalizing symptoms may be established in the neonatal period; this may also increase future risk for mood disorders as in older populations connectivity with the anterior insula relates to depressive symptoms, connectivity with the dorsal anterior cingulate relates to generalized anxiety, and the medial prefrontal cortex is related to behavioral inhibition. They also found that full-term and very preterm infants (VPT) had changes in the amygdala: positive correlations with subcortical and limbic structures and negative correlations with cortical regions, although magnitudes were decreased in VPT infants.[11]
Research results regarding hormonal influences during pregnancy and the neonatal period suggest that maternal endocrine activation during pregnancy (eg, exposure to ACTH, dexamethasone, or conditions that cause their release) and/or early separation or loss (eg, the neonate not being raised by the original primary caregiver) may result in lower cortisol levels overall and may correlate later in development with clinically significant symptoms of anxiety, learned helplessness, and depression.
Recent research evidence indicates that anxiety disorders in general, and separation anxiety specifically, are linked to dysregulation in the fear and stress response system in the brain and are one of the most common causes of school refusal.[12, 13]
Studies show that children of adults with anxiety disorders have higher rates of anxiety disorders. Experts have postulated that early and traumatic separation from the attachment figure (as well as a family history of anxiety disorders or depression in first-degree relatives) may increase the likelihood of the child and, later on, the adolescent or adult developing separation anxiety disorder, school phobia, and depressive-spectrum disorders.[14, 15]
Examples of early and traumatic separation include a prolonged stay away from the primary caregiver during the neonatal period; later sudden hospitalization; early loss of attachments because of death or divorce; or an interactive pattern with an over-protective, needy, or depressed parent.
In addition, some children may be more vulnerable to separation anxiety based on their temperament (ie, level of anxiety dealing with new situations).[10]
The prevalence of school refusal and separation anxiety disorder ranges from 1.3% in individuals aged 14-16 years to 4.1-4.7% in children aged 7-11 years, with an average prevalence rate of 2-4%. As many as one third of children with separation anxiety disorder have comorbid depressive disorder, and as many as 27% have another disruptive behavior disorder, such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, or conduct disorder.
In 1987, Burke et al reported that 5% of school-aged children refuse to attend school.[16] In 2005, the Centers for Disease Control and Prevention (CDC) prioritized the identification of the cause behind students not graduating high school. According to the report, as many as 40% of students who do not graduate high school have a diagnosable mental health disorder; as many as one half of those individuals may have anxiety disorders, such as posttraumatic stress disorder (PTSD) and school phobia.
In 2003, Egger et al reported that among children with anxious school refusal and truancy, as many as 88% had a psychiatric disorder.[14] Children with a history of pure truancy had high rates of oppositional defiant disorder (odds ratio, 2.2), depression (odds ratio, 2.6), and conduct disorder (odds ratio, 7.4). Anxious school refusal and truancy are distinct, but not mutually exclusive, disorders; thus, accurate diagnosis of comorbid conditions is important.
In 2001, McShane reported that one half of 192 adolescents with school refusal had a positive family history of psychiatric illness; those admitted for inpatient treatment were more likely to have a diagnosis of comorbid mood disorder and a maternal history of psychiatric illness.[17]
Scales such as the School Refusal Assessment Scale-Revised (SRAS-R) should be helpful in determining specifics of incidence and whether response to treatment differs among populations with low socioeconomic status, including ethnic minorities, with the goal being more accurate and earlier identification and prevention of school refusal.[18]
Anxiety-related school refusal is highly associated with other psychiatric disorders and generally begins when the child first enters school (age 5-6 y) and increases at age 10-11 years, at which time truancy begins. School nonattendance( especially when it intensifies) and truancy are associated with an increased risk for social problems such as school failure, unemployment, drug misuse, and delinquency, and there are significant relationships between parenting style, relative poverty, living in socially disadvantaged areas, attitudes towards school, the quality of the school system, and the quality of peer interactions.[19, 20]
In 1990, Bowen et al reported a 2.4% overall prevalence rate.[21]
Up to 60% of students at secondary schools in Germany report having avoided attending school for several hours or even a whole day over the course of their schooling. Proportionally more students in Germany compared with the rest of Europe (in 2006, about 76, 000; about 8% of the total) do not graduate secondary school.[15]
As previously mentioned, physical/somatic symptoms (especially frequent in older children and adolescents), such as dizziness, lightheadedness, nausea, stomachache, cramps, vomiting, muscle aches, or palpitations, may be present and problematic in individuals with separation anxiety.
A recent Australian study[22] found poorer overall child functioning at age 2-3 years in the context of overprotective mothering, likely due to higher maternal separation anxiety behaviors.
Extremely rare instances of mortality occur in severe separation anxiety. In "mothering to death" cases in the United Kingdom, the primary caregiver of an initially physically healthy child (generally an only child) interacted with the child in such a way that the child was perceived and behaved as physically ill and helpless; as adults, these children functioned as dependent and feeble individuals.
In one such case in the United Kingdom, the child became disabled and died.[23] This example is reflective of unchanging dysfunctional parent-child interaction at home.
Mortality generally results from associated major depression that may lead to suicide.
No specific differences in prevalence rates are noted for specific racial or cultural groups.
Somewhat increased incidence has been reported among close-knit families of lower socioeconomic status, as well as among single-parent families.
The prevalence of separation anxiety disorder is slightly greater in females than in males. The prevalence of school refusal is approximately equal between males and females.[21, 24]
Mean onset of separation anxiety disorder is at age 7.5 years. Mean onset of school refusal is at age 10.3 years.
Separation anxiety disorder is most frequent among younger children. One study lists prevalence rates for children aged 7-11 years at 4.1%; the same study lists prevalence rates for children aged 12-14 years at 3.9% and a prevalence rate of 1.3% for adolescents aged 14-16 years.
Separation anxiety disorder may wax and wane over a period of years. Approximately 30-40% of affected individuals have continued psychiatric symptoms into adulthood. Some studies have indicated as that as many as 65% of individuals with separation anxiety disorder have a comorbid anxiety disorder.[25]
The prognosis is good with early detection and treatment involving the family of the child.
Note that prevention of separation anxiety and school refusal begins with professional recognition of excessive attachment disorder and dynamics. Such prevention begins during yearly checkups in the pediatrics office, with discussions of healthy separation techniques. Educate families regarding healthy ways to deal with the inevitable stresses that occur in families with children and healthy ways to deal with sibling rivalry.
Weekly individual and family behavioral therapy, including cognitive-behavioral methods, is recommended to practice overcoming resistance to normal separation as well as to practice communicating differently as a family.
Recommend support for parents who may also have concurrent mental health or substance abuse issues. Address family violence prevention. Address any parental issues related to a sense of loss or feeling of abandonment or loneliness once the child or adolescent returns to a normal level of functioning and no longer requires the intense level of interaction with the parent or parents.
A patient’s family frequently reinforces separation anxiety symptoms. For example, when the family experiences a major life stress or illness and the child expresses mild refusal to leave the primary caregiver (who may be anxious, distressed, or depressed), the child is not firmly encouraged to appropriately separate and instead is rewarded either overtly or covertly for refusal to separate (eg, when the child who refuses to leave is given extra attention or when the child who refuses to attend school is excused by the parent). In these instances, the parent does not clearly give the child the task of developing strategies to adapt to the separation.
As a result, psychoeducation with the family is important so that the child is rewarded for developmentally appropriate actions and does not receive secondary gain from the symptoms of school refusal or separation anxiety disorder.
For patient education information, see eMedicineHealth's Mental Health Center, as well as Anxiety, Panic Attacks, Hyperventilation, and School Refusal.
The onset and development of symptoms, as well as their context, help to establish the diagnosis of anxiety disorder. Noting whether anxiety is stimulus-specific, spontaneous, or anticipatory; whether the symptoms result in avoidant behavior (ie, degree of constriction of daily life) that is clinically significant and disabling; and whether social and familial reinforcers of symptoms are present is helpful.
In assessing patients with separation anxiety, school refusal, or both, the patient’s history must be obtained from multiple informants, including the patient, parents or caregivers, and other pertinent persons, such as teachers and coaches. Screen for features of depression (eg, anhedonia, insomnia, feelings of worthlessness) and ask the child directly about symptoms.
Pertinent educational, developmental, and family or social history should be obtained, including any family history of anxiety disorders and a history of separations and losses, school attendance, academic functioning, presence of environmental stressors, the patient’s degree of involvement with his or her peer group, and the patient’s social competence.
Separation anxiety disorder manifests slightly differently in different age groups. Children younger than 8 years tend to present with unrealistic worry about harm to their parents or attachment figures and school refusal.
Children aged 9–12 years tend to present with excessive distress at times of separation (eg, sleepaway camp, overnight school trips).
Adolescents aged 12–16 years more commonly present with school refusal and somatic problems involving autonomic symptoms, such as headaches, dizziness, lightheadedness, sweatiness, or GI or musculoskeletal symptoms (eg, stomachache, nausea, cramps, vomiting, or muscle or body aches [such as back pain or muscle tension]).
In general, younger children may be referred more often than older children, because the somatic symptoms seen in adolescents may not be as clearly correlated with situations of imminent or actual separation from attachment figures.
Family history is extremely helpful in elucidating precipitating factors and should be obtained in a therapeutic manner so that the family feels that the interviewer understands the emotional stress and is responsive to it.
In the family assessment, the style of relatedness of the family should be described; enmeshed versus disengaged family stressors, including losses (especially if proximate to the start of symptoms), and family history of anxiety, alcoholism, somatoform, or mood disorders should be noted.
Family history of school refusal (especially in mothers) is also helpful because it may correlate with separation anxiety disorders in the child.
A history of prominent anxiety symptoms in either the child or parents in certain situations (eg, preanesthesia, perianesthesia) may correlate with phobic or anxious symptoms in the child at a different time (ie, postanesthesia).
Generally, somatic symptoms associated with separation anxiety, such as palpitations or abdominal pain, have no clear physical origin. However, a careful physical examination with appropriate blood work is recommended to rule out physical causes, including occult serologic streptococcal infection, hyperthyroidism, hypothyroidism, mitral valve prolapse, asthma, or GI infection, inflammation, bleeding, or ulceration.
Assure the child and his or her family that somatic symptoms are indicators of a problem that is serious and requires attention. Psychological interventions should proceed simultaneously with medical evaluations.
Transient developmental fears (eg, fear of the dark) are generally normal and do not interfere with normal functioning or result in long-term developmental difficulty; however, studies show a subgroup of children who do not meet the criteria for diagnosis of an anxiety disorder but who may have substantial impairment later in life. Studies of children who, in first grade, present with significant symptoms of anxiety (enough to cause clinically significant impairment in social and academic functioning) reflect a correlation with significant impairment in reading and math achievement 5–6 years later. Complications of separation anxiety can also include the following: truancy, major depression, and substance abuse or dependence. Long-term follow-up studies of children successfully treated for school refusal because of separation anxiety reveal that some children have continued impairment of social functioning (ie, social and affective constriction), despite having returned to school. This may reflect the long-term impairment and morbidity and unchanging dysfunctional parent-child interaction at home.[25, 26]
To help prevent secondary complications, do not be overzealous in the workup for a physical etiology of the somatic problems; however, do be prudent.
Various structured or semistructured interview scales aid in confirming a diagnosis of separation anxiety, while laboratory studies and physical examinations help to rule out other symptom sources.
Sleep studies may have utility if a significant history of difficulty initiating or maintaining a normal sleep cycle is reported. One study used parent questionnaires to elucidate cross-sectional and longitudinal relationships among variables related to sleep patterns and both social-emotional problems (i.e., internalizing, externalizing, and dysregulation) and healthy social development (i.e., social competence) at 6, 12, and 18 months across 5 cohorts of children for a total of 117 mother-child dyads. Young children were more likely to have higher anxiety, depression, and separation distress scores when they slept less total time and also went to sleep later; the study did not determine the directionality of the association.[27]
Consider the following tests to rule out possible conditions in patients with suspected separation anxiety, school refusal, or both only when clinically pertinent and age relevant.
Triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) tests can be run to rule out thyroid abnormalities.
A 2-hour postprandial glucose can be performed to rule out type I or type II diabetes mellitus.
Titer measurements can be performed for antistreptococcal antibodies (ASO titer), Babesia (to rule out babesiosis), Lyme disease, and rickettsial illness (eg, Rocky Mountain spotted fever). This can be especially important in patients with a history that includes fever, rash, or sore throat with incomplete or no treatment (with antibiotics), and a history of acute change in personality or anxiety or obsessive features.
Blood levels of lead and other heavy metals, such as mercury, can be measured to rule out lead or heavy metal poisoning (abdominal pain).
A complete blood count (CBC) and measurements of hematocrit (Hct) levels and hemoglobin (Hgb) concentrations can be performed to rule out the presence of anemia (for example, as a cause of abdominal pain.)
Urine screening for drugs of abuse can be used to rule out stimulant or steroid abuse.
If other information suggests brain tumor or seizure disorder, perform appropriate imaging studies (eg, magnetic resonance imaging [MRI], computed tomography [CT] scanning, positron emission tomography [PET] scanning).
Obtain an echocardiogram with functional examination to rule out mitral valve prolapse or other structural cardiac abnormalities (eg, regurgitation).
Functional behavioral assessment should include specific observations of the child's symptoms and behaviors; note frequency, intensity, location, and proximity to caregiver.
Perform a structured or semistructured interview to determine whether a risk of suicidal ideation is present.
Structured or semistructured interview scales are extremely helpful in confirming the clinical diagnosis and should be administered by clinically experienced personnel (eg, child and adolescent psychiatrists, developmental and behavioral pediatricians, clinical psychologists, social workers). The following are examples of structured or semistructured interview scales used to assess anxiety disorders in children and adolescents:
The goal of treatment is to facilitate the child returning to normal developmental functioning. The child with separation anxiety needs to be able to tolerate normal separation from caregivers without distress or impairment of functioning. The child or adolescent with concomitant school refusal should return to school as quickly as is medically and socially possible and consistently attend school without subjective experiencing of distress.
Placing the child on homebound instruction is contraindicated because it may prolong the child's symptoms and increase the severity of symptoms because of secondary gain increases.
Return to other normal duties should be recommended gradually to prevent the child and family from experiencing intensified anxiety and prematurely dropping out of treatment.
Relaxation techniques with participant modeling and subsequent reinforced practice are often more effective when used before cognitive-behavior therapy techniques, because the patient is more likely to continue with therapy if anxiety does not increase at the start of therapy.[28]
Cognitive behavioral therapy is associated with the shortest duration of treatment (mean 6 mo) and best outcome, with some studies showing 83% of children attending school at 1-year follow-up.
Cognitive therapy attempts to restructure the child's thoughts and actions into a more assertive and adaptive framework. Also included are systematic desensitization and exposure and operant behavioral techniques to facilitate successful separation of the child from the parent, as well as a rapid return to typical life, such as attendance of school close to 100% of the time.
Identification and recognition (including being able to articulate the feeling) of somatic symptoms related to anxiety, as well as the creation of a new functional response to deal with symptoms, are central to successful behavior change.
Modeling, role-playing, relaxation techniques, and reward systems for behavior change are examples of cognitive-behavioral therapies.
The "Coping Cat" manualized cognitive behavioral therapy approach has been useful and cross-culturally effective; this technique can be performed on a computer, which is often more appealing to children.[29]
In the psychodynamic approach, a child-oriented and trained mental health professional usually delineates the psychological rationale (whether conscious or unconscious) for the child's symptoms and behaviors. Individual psychodynamic therapy (play used as the modality for younger or nonverbal children) at least twice a week results in the best outcome (>70% improvement). More frequent treatment of 3-4 times per week for 6 months helps the child or adolescent work through feelings and reactions to the upsetting situations and encourages the child or adolescent to behave in a different manner.
Family therapy includes obtaining history of family members for psychosomatic symptoms, anxiety disorders (eg, agoraphobia), depression, and alcoholism as well as facilitating communication to change dysfunctional patterns within the family. These patterns may serve to maintain the child feeling unable to separate from attachment figures (eg, loyalty conflicts). These family actions may cause the family to unwittingly encourage the child in the ill role.
Social therapy includes gathering history regarding other factors that may have an impact on or explain the child's behavior. Determine if the child is refusing school for nonseparation issues, such as avoiding the school bully or gang, hiding academic problems (ie, developing abdominal pain on test day only), or refusing school because of anticipation of school failure. (See History.)
These symptoms usually reflect other factors that contribute to the child not wishing to attend school, such as learning disorders or inappropriate school placement.
Pharmacologic therapy should be used along with other therapies in an adjunctive manner when the level of functional impairment is moderate to severe, to prevent further loss of function and to facilitate or hasten positive outcomes of behavioral interventions. (See Medications.)
Before and during a trial of fluoxetine (Prozac), the only selective serotonin reuptake inhibitor (SSRI) approved by the US Food and Drug Administration (FDA) for use in patients younger than age 18 years, the clinician must closely monitor the patient for new-onset self-harm or suicidal behavior or ideation.
Non-FDA approved agents that may be helpful to reduce anxiety include beta-adrenergic blocking agents (contraindicated in persons with asthma), alpha-adrenergic agonists (eg, clonidine, guanfacine), SSRIs (eg, sertraline), and nonbarbiturate agents for anxiety (eg, buspirone, gabapentin, hydroxyzine).
Placebo-controlled studies by the FDA have shown that the risk of self-harm and potentially suicidal behavior is 1.5-3.2 times greater with paroxetine or venlafaxine and other serotonin-norepinephrine reuptake inhibitors (SNRIs), except for fluoxetine, sertraline, and citalopram, than with placebo. The FDA requires a black box warning because of this increased risk.
Although initial studies showed improved response to paroxetine (Paxil), this medication should be used only in patients older than 18 years (for adjunctive pharmacologic treatment) and with caution, because it must be dosed twice daily to prevent withdrawal symptoms that seem to be associated with increased risk of new-onset suicidality or self-harm.
Future directions may include the use of bumetanide to ameliorate maternal separation-induced susceptibility to stress.[30]
Research evidence[31] from fMRI studies of anxious youth that found altered behavioral performance on the dot-probe task (including the use of the dot replacing a neutral or fearful face[31] possibly due to altered neural mechanisms of threat disengagement) have led to current research trials targeting neural mechanisms of threat disengagement through the use of video games, by increasing integration across the rostrodorsal anterior cingulate cortex (rdACC) and limbic regions with the goal to be successful disengagement of threat reactivity in the rdACC.[32]
No diet has been proven helpful. No vitamin supplements have been proven helpful, although vitamin B-6 and magnesium seem to have been given to children with a multiplicity of behavioral disorders without benefit and potential harm (nerve impairment [anosmia], intestinal difficulties).
Consultation with child and adolescent psychiatrists or behavioral/developmental pediatric specialists is helpful to coordinate treatment efforts and reduce unnecessary medical procedures. This also helps in gathering a complete history, including information from parents, teachers, school staff, and peers.
Preparation of children before medical or surgical procedures to help them feel less helpless in the situation. Play therapy can be extremely helpful, especially for children who have had to undergo medical procedures or surgery.
Prevention of school anxiety and refusal includes the following activities:
The last item above, positive preparation, includes procurement of school supplies, arrangement of suitable familiar transportation for the child to get to school, and, possibly, the establishment, in advance, of phone time to call home to prevent undue anxiety, as well as to provide the child an opportunity to discuss any concerns or worries he or she may have related to starting or returning to school.
Medication treatment has proven effective as adjunctive treatment along with cognitive-behavioral therapy for separation anxiety and school refusal and may hasten return to normal activities. Medication as the only treatment should not be used initially as treatment for separation anxiety disorder.
Neuroleptics (ie, antipsychotic agents) are contraindicated in separation anxiety disorder. Cases of children with Tourette syndrome have been reported in which separation anxiety disorder develops after initiation of haloperidol or pimozide or other neuroleptic medication.
Associated weight gain with neuroleptics, particularly olanzapine, may increase later risk for potentially life-threatening cardiovascular disease due to persistent elevation of serum cholesterol and triglycerides, either because of the direct effect of the neuroleptic or secondarily because of the effects of weight gain on the turnover of cholesterol and related compounds in the body.
Other agents such as tricyclic antidepressants, selective serotonin reuptake inhibitors, anxiolytics, alpha-adrenergic agonists, and beta-adrenergic blocking agents have been used.
Future directions incliude the use of investigational agents such as bumetanide.[30]
Clinical Context: Imipramine inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neurons. Only imipramine is FDA-approved for panic disorder and use in children, although its usage in separation anxiety disorder is considered off-label. Intolerable adverse effects, including dry mouth, headache, narrow-angle glaucoma, cardiac complications (including rare events of sudden death), and partial or complete heart block, limit use. Extremely dangerous in overdose (deaths have occurred).
TCAs are not recommended as the first-line treatment of separation anxiety disorder and school refusal; however, the FDA has approved these medications for pediatric use as long as the substantial risk of mortality and morbidity in overdose and the potential for adverse cardiac effects (heart block, arrhythmias) are carefully monitored.
Clinical Context: This is the first SSRI ever used in children and adolescents. It has relative safety in overdose. Fluoxetine may cause more adverse GI effects than other currently available SSRIs.
This agent is available in liquid and cap form. Some case reports suggest that despite a possible association with rare occurrences of behavioral disinhibition, fluoxetine may be relatively safer in pediatric usage than are paroxetine or venlafaxine.
However, fluoxetine still carries risk and, therefore, has a "Black Box" warning. Do not use in children who are physically aggressive, have a family history of suicidal or parasuicidal ideation or behaviors, or are at increased risk of self-harm.
Clinical Context: Sertraline can be helpful in those who do not respond to fluoxetine; however, it is only FDA approved for pediatric obsessive-compulsive disorder, at a dose of 25 mg/day for (age 6-12 y) and 50 mg/day (age 12 y and up). Sertraline is FDA approved in adults for major depression, social anxiety disorder, posttraumatic stress disorder, obsessive-compulsive disorder, and panic disorder.
In the past, SSRIs were recommended as the first-line pharmacologic treatment for separation anxiety disorder because of efficacy; however, except for fluoxetine, the FDA has not approved most SSRIs for use in children younger than 12 years. Safety concerns because of complications (eg, increased risk of suicidal ideation or plan or disinhibition with aggression) preclude their current use in children and adolescents unless the patient's response is closely monitored (weekly basis for at least the first month) or unless the patient has had a past history of good response to SSRIs or SNRIs.
SSRIs have proven an unparalleled relative safety in overdose and have few cardiac or anticholinergic adverse effects. Efficacy studies of medication use for separation anxiety have shown promising results with respect to SSRIs and symptom remission. However, practitioners are advised against prescribing SSRIs, specifically paroxetine or venlafaxine, in children and adolescents.
Physicians are advised to be aware of the following information and use appropriate caution when considering treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of depressive illness. After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, with the exception of fluoxetine, which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the FDA issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed, because suicidality occurred in treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
A study of more than 65,000 children and adults treated for depression between 1992 and 2002 by the Group Health Cooperative in Seattle found that suicide risk declines, not rises, with the use of antidepressants.[33] This is the largest study to date to address this issue.
Currently, evidence does not associate OCD and other anxiety disorders treated with SSRIs with an increased risk of suicide.
Children at high risk for pediatric bipolar mood disorder (ie, positive first-degree family history for bipolar disorder or alcoholism along with history of aggression, impulsivity, and/or sleep disturbances related to initiation or maintenance of sleep) should be administered SSRIs with caution, because hypomania or frank mania or psychosis along with behavioral disinhibition may result.
Clinical Context: Alprazolam is a benzodiazepine and it is not recommended for prolonged use in children or adolescents because of concerns regarding drug dependance and tolerance. Use alprazolam for the shortest duration (< 2-3 wk to prevent addiction) and gradually taper it to prevent symptoms of withdrawal that could become potentially life threatening (ie, status epilepticus).
Clinical Context: Buspirone has been approved for use since 1986 in adults for anxiety, and its mechanism of action may be stimulating 5-HT1A and 5-HT2 receptors, as well as other minor effects on dopamine D2 receptors. Unlike benzodiazepines, it does not cause sedation. It is available in 5 strengths (5, 7.5, 10, 15, and 30 mg) and generally should be given in 2 or 3 divided doses starting at 10-15 mg/day, not to exceed 60 mg/day.
Do not take buspirone with warfarin (Coumadin) or grapefruit juice, owing to an increased risk of bleeding or elevated levels of buspirone. Buspirone is primarily metabolized by the liver, so medications that interfere with liver metabolism (nefazodone, erythromycin, itraconazole, rifampin) can potentially cause toxic or subtherapeutic levels of buspirone. It is not FDA approved for use in children or adolescents.
These agents reduce anticipatory and acute situational anxiety, as well as reduce muscle tension symptoms. They reduce symptoms in panic disorder. Anxiolytic agents are not the first-line treatment in children or adolescents because of concerns regarding drug dependence, withdrawal symptoms, and tolerance.
Clinical Context: Diphenhydramine competes with histamine for H1-receptor sites on target cells in the gastrointestinl tract, blood vessels and respiratory tract. Used as a sedative to establish proper sleep patterns. It is available in syrup, strip, liquid, solution, chewable, and cap formulations.
Clinical Context: Hydroxyzine competes with histamine for H1-receptor sites on target cells in the gastrointestinl tract, blood vessels and respiratory tract. It is FDA approved for use in children younger than 6 years (at 50 mg/day PO) and in children older than 6 years (at 50-100 mg/d PO) for short term use for anxiety, especially anxiety associated with medical procedures.
No controlled studies are available to evaluate the efficacy of antihistamines in the treatment of separation anxiety; however, possible adverse effects include a decrease in sleep latency and in midsleep awakenings.
Clinical Context: Propranolol is a nonselective beta-adrenergic blocker. The drug blocks adrenergic stimulation that may cause the physiologic symptoms of anxiety and may thus be helpful for decreasing the severity of somatic anxiety symptoms.
However, do not use propranolol in patients with asthma. In addition, the drug may cause unpleasant cardiovascular and GI adverse effects and is not the drug of choice, especially because hypotension and/or cardiac block can develop.
Initiation of therapy should be performed with close monitoring of blood pressure to prevent hypotensive crisis. Do not discontinue propranolol abruptly, because this may precipitate hypertensive crisis.
These block the physiological symptoms of anxiety and inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation. Do not use in patients with asthma because they may precipitate an acute asthmatic crisis.
Clinical Context: Gabapentin is a membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-amino butyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Gabapentin is not FDA approved for use in children for anxiety, but it is FDA approved for use in children aged 3 year and older for seizure disorders (40 mg/kg/day; with a half-life of 5-7 h, necessitating tid dosing). Gabapentin is FDA approved for use in adults with neuropathic pain or seizures; however, some concern exists about the possible addictive potential with this medication.
Clinical Context: Guanfacine stimulates alpha2A-adrenergic receptors, which reduces sympathetic nerve impulses and results in a reduction of sympathetic outflow.
Clinical Context: Clonidine is a central alpha-adrenergic agonist that stimulates alpha2-adrenoreceptors in the brain stem and activates an inhibitory neuron, resulting in a decrease in vasomotor tone and heart rate.
Alpha-adrenergic agents such as clonidine and guanfacine (Tenex) are not FDA approved for use in children but may be effective for anxiety, especially social anxiety associated with performance anxiety; children may be more likely than older adolescents or adults to have adverse reactions (eg, new-onset hallucinations, paradoxical excitation) to these agents.