eMedicine Specialties > Pediatrics: Developmental and Behavioral > Medical Topics

Anxiety Disorder, Separation Anxiety and School Refusal: Treatment & Medication

Author: Bettina E Bernstein, DO, Assistant Professor, Department of Psychiatry, Philadelphia College of Osteopathic Medicine; Private Practice at the Wynnewood House; Consultant, Child Guidance Resource Centers, Early Elementary Education Program, Clinical Affiliate, Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia
Contributor Information and Disclosures

Updated: Dec 3, 2008

Treatment

Medical Care

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 consistently attend school without subjective experiencing of distress. Placing the child on homebound instruction is contraindicated.

The multidimensional model of treatment includes the following approaches:

  • 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.11
  • 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.10
  • 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.12
    • 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 those younger than 18 years, the clinician must closely monitor the patient for new-onset self-harm or suicidal behavior or ideation.
    • Recent 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 had shown improved response to paroxetine (Paxil), this medication should be used only in those 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.
  • In the psychodynamic approach, a child-oriented and trained mental health professional usually delineates the psychologic 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. These symptoms usually reflect other factors that contribute to the child not wishing to attend school, such as learning disorders or inappropriate school placement.

Consultations

Consultation with child and adolescent psychiatrists or behavioral/developmental pediatric specialists is helpful to coordinate treatment efforts and reduce unnecessary medical procedures. This helps in gathering a complete history, including information from the parents, teachers, school staff, and peers.

Many specific structured and semistructured scales for anxiety disorders are used by mental health professionals (see Other Tests). They include the MASC from Duke University, the Screen for Child Anxiety Related Emotional Disorders (SCARED) from the Western Psychiatric Institute and Clinic, the Selective Mutism Questionnaire, the Separation Anxiety Test from the University of Washington, and the DICA. The specific anxiety scales are not diagnostic but can be helpful for measuring response to therapeutic interventions such as medications and cognitive-behavioral therapy.

Diet

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, intestinal difficulties).

Activity

No restrictions on activity apply.

Medication

Medication treatment has proven effective as adjunctive treatment along with cognitive-behavioral therapy for both 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 turnover of cholesterol and related compounds within the body.

Antidepressant agents

Historically, tricyclic antidepressants (TCAs) such as imipramine have been used for years in children as treatment of enuresis. However, concerns have arisen regarding their safety in these patients because cases of sudden cardiac death have occurred despite monitoring of serum blood levels and ECGs. Furthermore, other adverse effects have been noted, including hypotension, dry mouth, and glaucoma.

TCAs, such as imipramine (Tofranil), are not recommended for 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 is carefully monitored.

In the past, SSRIs have been recommended for first-line pharmacologic treatment of separation anxiety disorder because of efficacy; however, except for fluoxetine (Prozac), the FDA has not approved most selective serotonin reuptake inhibitors (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.

Prozac (fluoxetine) is currently the only SSRI approved for use in children and adolescents and at this time is only approved for the treatment of depression or obsessive-compulsive disorder. SSRIs have proven unparalleled relative safety in overdose and 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, except fluoxetine (Prozac), 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 (both 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 both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.

However, a recent 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.13 This is the largest study to date to address this issue.

Currently, evidence does not associate obsessive-compulsive disorder (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.


Fluoxetine (Prozac)

First SSRI ever used in children and adolescents. Relative safety in overdose. May cause more GI adverse effects than other SSRIs currently available. Available in liquid and cap form. Some case reports suggest that despite possible association with rare occurrences of behavioral disinhibition, fluoxetine may be relatively safer in pediatric usage than paroxetine or venlafaxine although still carries risk, hence, the "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.

Adult

20-40 mg PO qd

Pediatric

2-5 mg PO every am initially; may increase q2-4d to prevent agitation; not to exceed 20 mg/d in younger children
Doses as high as 60 mg/d have been administered to particularly anxious school-aged children and adolescents, but this should be administered in consultation with a professional who has advanced expertise in the psychopharmacology of drugs in mental health and only with close monitoring of the patient's status

Inhibits CYP2D6 and CYP3A4, may increase toxicity of 2D6 substrates (eg, thioridazine, theophylline) and 3A4 substrates (eg, benzodiazepines, pimozide, cisapride, trazodone)
Increases toxicity of MAOIs and highly protein-bound drugs; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan, sumatriptan), discontinue other serotonergic agents at least 2 wk prior to SSRIs

Documented hypersensitivity; concurrent administration with MAOIs or administering within 14 d of discontinuing MAOIs; concurrent administration with thioridazine (ie, increased QTc interval); children at high risk for pediatric bipolar disorder (first-degree relative with bipolar disorder or alcoholism; history of aggression or impulsive outbursts, self-harm, suicidal behavior or ideation, or difficulties with initiation or maintenance of sleep)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

The safety of SSRIs and SNRIs during the first trimester of pregnancy is controversial; avoidance of usage would be prudent, if possible, during the first trimester (risk of increased birth defects).
Newborn infants exposed to SSRIs during the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; pregnancy is a relative contraindication; seizure disorder is a relative contraindication; use with caution in children at risk for pediatric bipolar disorder (first-degree relative with bipolar disorder or alcoholism and/or history of aggression or impulsive outbursts and/or difficulties with initiation or maintenance of sleep)
Relatively safe in overdose; however, because of the long half-life, the duration of respiratory depression or coma may be prolonged up to weeks; not recommended in bulimia (may worsen alteration in electrolyte balance) unless extremely close medical supervision is given


Imipramine (Tofranil)

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. Only imipramine is FDA approved for panic disorder and use in children. Usage in separation anxiety disorder is considered off-label. Intolerable adverse effects, including dry mouth, narrow-angle glaucoma, headache, cardiac complications, including rare events of sudden death, and partial or complete heart block, limit use. Extremely dangerous in overdose (deaths have occurred).

Adult

10 mg/d PO, increase by 10 mg q2-4d for 2 wk, then by 25 mg q2-3d; not to exceed 100 mg/d hs

Pediatric

Not established; recommended dose is 1.5 mg/kg/d PO, with dosage increases of 1 mg/kg q3-4d; not to exceed 5 mg/kg qd or divided bid/qid
Adolescents: 25-50 mg/d PO initially with dosage increases prn; not to exceed 100 mg/d

Increases toxicity of sympathomimetic agents such as isoproterenol and epinephrine by potentiating effects and inhibiting antihypertensive effects of clonidine

Observe the patient closely for new-onset suicidal or homicidal or self-injurious behavior especially if younger than 24 years old (FDA black box warning)
Documented hypersensitivity; narrow-angle glaucoma; acute recovery phase following myocardial infarction; current use of MAOIs or fluoxetine or use in previous 2 wk

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, glaucoma, hyperthyroidism, or in those receiving thyroid replacement; overdose has resulted in death

Anxiolytic agents

These agents reduce anticipatory and acute situational anxiety, as well as reduce muscle tension symptoms. Reduce symptoms in panic disorder. They are not first-line treatment in children or adolescents because of concerns regarding drug dependence, withdrawal symptoms, and tolerance.


Alprazolam (Xanax)

Not recommended for prolonged use in children or adolescents because of concerns regarding drug dependance and tolerance. Use for shortest duration (<2-3 wk to prevent addiction) and gradually taper to prevent symptoms of withdrawal that could become potentially life threatening (ie, status epilepticus). Studies of clonazepam showed it to be no more effective than placebo for the treatment of separation anxiety disorder.

Adult

0.25-6 mg/d PO divided bid/tid

Pediatric

<18 years: Not approved by the FDA for use
Not established, limited data suggest 0.04 mg/kg/d PO in divided doses; gradually titrate upward to desired effect, typical maintenance dose is 1 mg/d PO divided bid/tid; not to exceed 2 mg/d

Caution because drug is catalyzed at CYP3A; thus, clearance of alprazolam is altered, which can result in additive CNS or respiratory depression when administered with drugs that inhibit CYP3A (eg, antihistamines, propoxyphene, diltiazem, ketoconazole, itraconazole, nefazodone, PO contraceptives, phenobarbital, alcohol, fluvoxamine, fluoxetine, cimetidine, nicardipine, nifedipine, cyclosporine, amiodarone, ergotamine, isoniazid, erythromycin, clarithromycin, propoxyphene, fluoxetine, herbal Kava Kava, herbal valerian root, herbal St John's Wort, grapefruit juice)
Caution with coadministration of drugs causing respiratory depression (eg, opioid analgesics, alcohol)

Documented hypersensitivity; severe respiratory depression; narrow-angle glaucoma; preexisting hypotension; family history of substance abuse/dependence; uncontrolled seizure disorder; history of behavioral disinhibition

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Discourage the operation of heavy machinery while beginning this medication; do not discontinue suddenly because a potentially fatal withdrawal syndrome, including status epilepticus, may result; do not administer to a person who is at risk for behavioral disinhibition, depression, or psychosis; this medication is potentially fatal in overdose and should be administered in the smallest amounts and dispensed in childproof containers

Antihistamines

No controlled studies are available to evaluate efficacy in separation anxiety disorder; however, possible adverse effects include a decrease in sleep latency and in mid sleep awakenings.


Diphenhydramine (Benadryl, Simply Sleep)

Used as sedative to establish proper sleep patterns. Available as syr, chewable, and cap formulations.

Adult

10-50 mg PO hs; not to exceed 100 mg/d

Pediatric

10-25 mg PO hs

Potentiates effect of CNS depressants; because of alcohol content, do not give syr dosage form to patients taking medications that can cause disulfiramlike reactions; coadministration or use within 14 d may precipitate hypertensive crisis

Documented hypersensitivity; MAOIs

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause paradoxic excitation and hallucinations in children; therefore, with history of paradoxic reactions to similar medications, administer with caution; sedative effects may diminish with time, and increasing the dosage does not help; long-term studies of carcinogenesis or mutagenesis have not been performed; may exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur

Beta-adrenergic blocking agents

These block the physiological symptoms of anxiety and inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.


Propranolol (Inderal)

Do not use in patients with asthma. Blocks the physiologic symptoms of anxiety and, thus, may be helpful for decreasing the severity of the somatic symptoms of anxiety. May cause unpleasant cardiovascular and GI adverse effects and is not the DOC, 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 abruptly because this may precipitate hypertensive crisis. Available as tabs, SR, and liquid preparations.

Adult

10-40 mg/d PO divided bid

Pediatric

0.05-1 mg/kg/d PO divided bid; not to exceed 20 mg/d

Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease propranolol effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase; alcohol may decrease absorption

Documented hypersensitivity; uncompensated congestive heart failure; bradycardia, cardiogenic shock; AV conduction abnormalities; asthma; depressive symptomatology (relative contraindication)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Lower dosage in patients with Down syndrome (trisomy 21) because they may have increased levels due to altered bioavailability; close monitoring of blood pressure is important because frequently, at the start of treatment, patients may experience dizziness, which could potentially result in falling; discourage the operation of heavy machinery while initially taking this medication because it may cause drowsiness or decreased mental acuity for some; use with caution in patients with family history of depression because this medication may exacerbate depressive symptoms
Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely

More on Anxiety Disorder, Separation Anxiety and School Refusal

Overview: Anxiety Disorder, Separation Anxiety and School Refusal
Differential Diagnoses & Workup: Anxiety Disorder, Separation Anxiety and School Refusal
Treatment & Medication: Anxiety Disorder, Separation Anxiety and School Refusal
Follow-up: Anxiety Disorder, Separation Anxiety and School Refusal
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

school phobia, separation anxiety disorder, excessive anxiety, severe distress, tantrums, nightmares, extreme homesickness, psychosomatic symptoms, clinging behavior, daycare, depression, suicide, truancy, skipping school, school refusal, learned helplessness, transient developmental fears, posttraumatic stress disorder, anhedonia, insomnia, feelings of worthlessness, occult serologic streptococcal infection, hyperthyroidism, hypothyroidism, mitral valve prolapse, asthma, depressive-spectrum disorders, diabetes mellitus, Lyme disease, Rocky Mountain spotted fever

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Contributor Information and Disclosures

Author

Bettina E Bernstein, DO, Assistant Professor, Department of Psychiatry, Philadelphia College of Osteopathic Medicine; Private Practice at the Wynnewood House; Consultant, Child Guidance Resource Centers, Early Elementary Education Program, Clinical Affiliate, Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia
Bettina E Bernstein, DO is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry and American Psychiatric Association
Disclosure: Nothing to disclose.

Medical Editor

Angelo P Giardino, MD, PhD, Clinical Associate Professor, Department of Pediatrics, Baylor College of Medicine; Medical Director, Texas Children's Health Plan, Inc
Angelo P Giardino, MD, PhD is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, American Professional Society on the Abuse of Children, Harris County Medical Society, Helfer Society, and International Society for Prevention of Child Abuse and Neglect
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

CME Editor

Carrie Sylvester, MD, MPH, Director of Education in Child and Adolescent Psychiatry, Professor, Departments of Psychiatry and Pediatrics, Northwestern University Medical School
Carrie Sylvester, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, American Medical Women's Association, American Psychiatric Association, and American Society for Adolescent Psychiatry
Disclosure: Nothing to disclose.

Chief Editor

Caroly Pataki, MD, Professor of Clinical Psychiatry and Behavioral Sciences, Department of Psychiatry, Division Chair, Child and Adolescent Psychiatry, Director of Training, Child and Adolescent Psychiatry Residency Program, University of Southern California Keck School of Medicine
Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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