Pediatric Panic Disorder

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Background

The presence of recurrent panic attacks is an essential feature of panic disorder. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), panic attacks feature prominently within the anxiety disorders, of which panic disorder is one.[1]

In panic disorder, the individual experiences recurrent unexpected panic attacks and is persistently concerned or worried about having more panic attacks or changes his or her behavior in maladaptive ways because of the panic attacks. A panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time 4 or more of the following symptoms occur:[1]  

The attack has a sudden onset and typically reaches a peak within 10 minutes. Panic attacks can be (1) unexpected, that is, not associated with a specific trigger; (2) situationally bound, that is, almost always occurring on exposure to, or in anticipation of, a specific trigger; or (3) situationally predisposed, which means they are more likely to occur on exposure to a trigger but are not invariably associated with that trigger. Situationally bound panic disorder is very similar to specific phobia except for the degree of the reaction. Unexpected and situationally predisposed panic attacks are the most frequent types in panic disorder. (See Etiology and History.)

In 1994, the American Psychiatric Association included panic disorder with agoraphobia and panic disorder without agoraphobia in the DSM-IV. (In prior DSM editions, the terms panic disorder and agoraphobia with panic attacks had been used to describe similar conditions.) In DSM-5, panic disorder and agoraphobia are two separate and distinct disorders.[1]

Although panic disorder is more frequent in older adolescents and adults, it does occur in children. It is an important disorder to consider, because unrecognized and untreated panic disorder can have a devastating impact on a child's life and can interfere with normal development, schoolwork, and relationships. (See Epidemiology and Prognosis.)

Complications

Somatic symptoms of panic disorder may lead to excessive and invasive examinations when appropriate mental health professional assessment is delayed.

Reluctance to go to school or engage in other age-appropriate activities may result from panic disorder.

Comorbid depression is not uncommon, and, in severe cases, children and adolescents may become suicidal.

Adolescents with panic disorder may self-medicate, leading to substance abuse.

Etiology

Biologic vulnerability in combination with stressful circumstances or events is hypothesized to contribute to the development of panic disorder. Studies have suggested a possible link between certain mutations of the gene for catechol-O-methyltransferase and the development of panic or anxious reactions in response to aversive stimuli, although no causational link has been proven.[2] There has been speculation that carriers of such polymorphisms may benefit from targeted interventions to prevent the development of panic pathology in adversarial situations.[2]  

In addition, children with parents who struggle with anxiety are at higher risk of developing anxiety. A possible genetic link to the development of anxiety also has been supported through twin studies. Parents who are anxious may contribute further to higher anxiety levels in their children by modeling anxious behavior and maladaptive coping. Behavioral inhibition, a temperamental style associated with avoidance of new stimuli, has been found to place children at risk for anxiety disorders.

Researchers do not believe, however, that all children of parents who are anxious also become anxious.

Other factors that may contribute to panic disorder are insecure attachment patterns, high levels of stress in the home, and the presence of stressful life events. In fact, the first panic attack often is preceded by a stressful event, such as the death of a parent or other significant person, a move to a new school, or any other significant, emotionally traumatic experience. Early studies suggest a link between separation anxiety and later development of panic disorder, but this appears to be a nonspecific risk factor for panic disorder or depressive disorder.

Some evidence suggests that children and adolescents who develop panic disorder tend to be hypersensitive to certain bodily sensations and interpret these sensations as dangerous when they may be harmless.[3]  There have been studies of fMRI imaging in panic disorder patients that demonstrate differential activation of the insula and brainstem neural circuitry. Such neurological findings suggest that the fear of cardiovascular and respiratory symptoms may represent a core feature of panic disorder.[4]  

However, prospective studies looking to predict which adolescents will develop panic disorders are lacking. One prospective survey suggested an association between development of major depression and panic disorder (and vice-versa).[5]

Epidemiology

In the general population, the 12-month prevalence estimate for panic disorder across the United States and several European countries is about 2%-3% in adults and adolescents.[1]

The median age at onset for panic disorder in the United States is 20-24 years. A small number of cases begin in childhood; the overall prevalence is low before age 14 years (< 0.4%).[1]

Females are more frequently affected than males.

Prognosis

The prognosis may be worsened when parents are unable to assist in their child's treatment or model adaptive coping/anxiety management because of their own untreated anxiety (or other psychiatric conditions).

In a clinical sample of 10 children who met the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for panic disorder, the recovery rate was 70% during a 3- to 4-year follow-up period. However, 30% of the children developed new psychiatric disorders.[6] This constitutes the worst prognosis for an anxiety disorder with onset in childhood or adolescence; nonetheless, the prognosis with ongoing treatment is unknown and may have become more favorable owing to developments in psychopharmacology and psychotherapy.

Without effective intervention, adolescent patients, especially those with comorbid agoraphobia, may experience an exacerbation of symptoms in adulthood. Serious adverse consequences include interpersonal, academic, and occupational impairments.[7]

Mortality and morbidity

Isolated panic disorder is uncommon in the pediatric population.[8] A careful screening for other anxiety, mood, trauma-related, and substance use disorders is particularly essential. Multiple coexisting disorders compound morbidity.

Panic disorder may be a marker for increased risk of suicide in individuals with co-occurring depressive disorder.

Panic disorder leads to psychological morbidity when the spontaneous attacks become associated with some place or event such that the patient develops increased anticipatory anxiety or phobic avoidance. (This is different from specific phobia, in which no spontaneous attacks are experienced and in which the phobic avoidance is confined to 1 thing or situation.)

Panic disorder is associated with a lifetime risk of increased morbidity and mortality from stress-related physical problems.

Patient Education

Psychoeducation should be part of the treatment process for panic disorder. Patient and parents should have a good understanding of the contributing and maintaining factors of anxiety. Also, they should be clear on the treatment goals, process, and expectations.

For patient education information, see the Anxiety Center, as well as Anxiety, Panic Attacks, and Hyperventilation.

History

Children with panic disorder may experience the following somatic symptoms during discrete panic attacks:

Patients also may have the above symptoms, to some degree, as symptoms of anticipatory anxiety or comorbid generalized anxiety disorder. Anxious muscle tension also can occur, with trembling, twitching, a feeling of shakiness, and muscle soreness or aches. Stomachaches and headaches may be the most frequent symptoms.

Diagnostic Criteria (DSM-5)

The DSM-5 criteria for panic disorder are as follows:[1]

Physical Examination

Children with panic disorder may have few physical findings, because the attacks rarely occur in the presence of a physician. Hyperventilation to the point of carpal-pedal spasm is rare.

Approach Considerations

Excessive medical workup without clear indication by history and physical examination is contraindicated because it can exacerbate anxiety.

The relatively rare medical causes of panic in pediatric patients, such as hyperinsulinemia or hyperthyroidism, should be documented with appropriate laboratory studies.

A comprehensive review of medications is indicated to ascertain the potential influence of any illicit or over-the-counter substances in the presentation of the patient’s symptoms.[12]

Structured Interview

A structured interview, such as the Anxiety Disorders Interview Schedule for DSM-IV Child and Parent Versions (ADIS-C/P), can be employed.

Questionnaires, such as the Revised Children's Manifest Anxiety Scale (RCMAS), the Multidimensional Anxiety Scale for Children (MASC),[13] and the Screen for Child Anxiety Related Emotional Disorders (SCARED),[14] child and parent versions, can be used to further assess anxiety symptoms.

The Anxiety Disorders Interview Schedule for Children is a comprehensive semistructured interview administered by clinicians to children age 7-17 years. It differentiates between each type of childhood anxiety disorder. It assures the collection of high-quality data, enables clinicians to indicate a primary or most-impairing diagnosis, and has good inter-rater reliability.

Preliminary studies have demonstrated the Autonomic Nervous System (ANS) Questionnaire as another screening test that is sensitive for panic disorder in the adolescent patient population.[7]

Self- and parent-report measures used in evaluating pediatric panic disorder include the School Refusal Assessment Questionnaire and the Social Phobia and Anxiety Inventory for Children.

Approach Considerations

Because of the frequent comorbidity of other diagnoses in pediatric patients, recent literature has proposed the employment of transdiagnostic interventions in the management of pediatric panic disorder.[8]

Support for the use of individual and family-based cognitive-behavioral treatment approaches for childhood anxiety disorders has been demonstrated in randomized, controlled trials.[15, 16, 17, 18]

Current guidelines recommend that the clinician and family form an active alliance in the treatment of children with panic disorder.[12]

Outpatient psychotherapy may be required for a few weeks to a year or longer.

Go to Pediatric Generalized Anxiety Disorder and Pediatric Obsessive-Compulsive Disorder for complete information on these topics.

Consultations

Consultation with a child psychologist, psychiatrist, or behavioral-developmental pediatrician is important for the evaluation and treatment of panic disorder.

Behavioral Therapy

Behavioral techniques often discussed in association with the treatment of panic disorder include deep breathing and relaxation, development of a systematic desensitization program, prolonged and carefully monitored exposure to negatively perceived stimuli, adaptive modeling, and contingency management. These techniques seek to change the way the child acts and reduce avoidance and the subjective experience of anxiety.[19]

Complementary cognitive techniques include developing a fear hierarchy, learning to identify and monitor feelings and bodily sensations, making accurate interpretations of situations and bodily sensations, and improving problem-solving skills.

Treatment may include developing a coping regimen and practicing using this regimen in the office and/or in vivo.

The importance of parental involvement in the treatment of childhood anxiety disorders has received attention, and such involvement is a necessary component to ensure success. The family-based component in the treatment of panic disorder can include contingency management, improved communication and problem-solving skills at the family level, and encouragement of effective coping through modeling.

The Coping Cat workbook is a cognitive behavioral therapy program for children that focuses on the identification feelings and somatic symptoms, the restructuring of negative thoughts into "coping self-talk," relaxation, problem solving, and self-monitoring. Acute cognitive behavioral therapy for children with panic disorder is typically provided over 12-16 sessions, with maintenance.

Activity

Children and adolescents with this disorder may need help learning to interpret physical reactions in response to exercise as normal and not a sign of an imminent panic attack.

Deterrence and Prevention of Panic Disorder

A consistent, stable, supportive home environment with parenting practices that promote self-confidence, self-esteem, and effective coping skills are important preventive measures.

Minimize psychosocial stressors or traumatic events when possible and provide rapid psychological intervention.

Parents and other significant people in the child's life should model adaptive problem-solving and coping skills.

Patient Monitoring

Follow-up care during medical treatment with a selective serotonin reuptake inhibitor (SSRI; eg, fluoxetine) includes monitoring pulse and paying particular attention to symptoms of hepatic dysfunction, seizures, and movement disorder.

Anorexia, gastrointestinal dysfunction, and headache tend to be possible transient adverse effects of SSRIs. Rashes may not be reported until they already have passed and tend to be coincidental with viral illness; thus, they should be assessed by a primary care physician familiar with the rash-producing illnesses currently occurring in the community.

For patients for whom medication is prescribed, regular follow-up care with a child and adolescent psychiatrist or developmental-behavioral pediatrician is necessary for the duration of treatment.

A diary of symptoms may be a helpful tool for a psychiatrist to monitor the progression of a child’s treatment.[12]

Medication Summary

Medication is adjunctive to psychological treatment of panic disorder.

The US Food and Drug Administration (FDA) has not approved the use of antidepressants for treating panic disorder in children and adolescents. Physicians considering this off-label option must document that the child and parents received sufficient informed consent regarding the use of these medications.

Current treatment guidelines recommend consideration of any physical illnesses present at the time of administering psychotropic medications. Medications that may be administered in a single dose and with minimum requirement for toxicological monitoring are preferred.[10]

SSRIs are currently the antidepressants of choice. These medications are powerful anxiolytics with a broader spectrum, such that comorbid affective disorders may also respond to treatment. Tricyclic antidepressants are not generally recommended for the treatment of panic disorder in children and adolescents because of their potential cardiotoxicity. In rare patients in whom symptoms are resistant to treatment, these drugs may be considered. The dosage and use of these agents for panic disorder is similar to their use in depressive disorder.

Presently, there are no randomized, controlled trials involving youth specifically diagnosed with panic disorder. A retrospective chart review of 18 children and adolescents treated with 5-40 mg/day of paroxetine for panic disorder demonstrated significant improvement in 15 of 18 patients, with only transient and mild adverse effects associated with higher doses.[20] An open case series documented the benefits of citalopram in school refusal with panic disorder.[21]

Benzodiazepines have a relatively favorable adverse effect profile but are not considered first-line medications in the treatment of panic disorder in children and adolescents. In some young children, these agents may cause behavioral disinhibition. In addition, a potential withdrawal syndrome can occur after prolonged use. Some benzodiazepines also have "street value" as drugs of abuse.

Buspirone (BuSpar), which is an anxiolytic unrelated chemically and pharmacologically to benzodiazepines, does not suppress panic attacks.

Monoamine oxidase inhibitors (MAOIs) are the most effective agents to manage panic attacks in adults. They are not used as first- or second-line agents in adults for the same reasons that they are not used in children or adolescents (ie, risk of hypertensive crisis, dietary restrictions).

Antihistamines and antipsychotics are not recommended for treatment of childhood-onset anxiety disorders.

Fluoxetine (Prozac)

Clinical Context:  Fluoxetine has had the longest use in children and adolescents. It is now available in generic preparations.

Its long half-life is an advantage and drawback. If it works well, an occasional missed dose is not a problem. If problems occur, eliminating all active metabolites takes a long time (ie, several weeks).

Adverse effects of SSRIs appear to be quite idiosyncratic; thus, relatively little reason exists to prefer one to another if dosing is started at a conservative level and advanced as tolerated.

Fluvoxamine (Luvox CR)

Clinical Context:  Fluvoxamine enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than tricyclic antidepressants.

Fluvoxamine has been shown to reduce repetitive thoughts, maladaptive behaviors, and aggression and to increase social relatedness and language use.

Sertraline (Zoloft)

Clinical Context:  Zoloft selectively inhibits presynaptic serotonin reuptake.

Paroxetine (Paxil, Pexeva)

Clinical Context:  Paroxetine would be unlabeled use. It is a potent selective inhibitor of neuronal serotonin reuptake and has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance dosing, make dosage adjustments to maintain the patient on the lowest effective dosage, and reassess the patient periodically to determine the need for continued treatment.

A retrospective chart review of 18 children and adolescents treated with 5-40 mg/day of paroxetine for panic disorder demonstrated significant improvement in 15 of 18 patients, with only transient and mild adverse effects associated with higher doses.[16]

Class Summary

These agents inhibit neuronal uptake of serotonin, thus potentiating serotonergic activity in the brain and down-regulating the potential for panic attacks. Fluoxetine is presented as an example. Several SSRIs are now available.

SSRIs are greatly preferred over the other classes of antidepressants. Because the adverse effect profile of SSRIs is less prominent, improved compliance is promoted. SSRIs do not have the arrhythmia risk associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.

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.

On October 15, 2004 the US Food and Drug Administration (FDA) issued a directive to all pharmaceutical companies, instructing them to include a black box warning label on all antidepressant medications (such as SSRIs). This decision was based on an analysis demonstrating that children and adolescents on antidepressant medications may have a small, but statistically significant risk of suicidal ideation. Initially, this risk was thought to increase during the first few months after initiating 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. This is the largest study to date to address this issue.

Currently, evidence does not exist to associate obsessive-compulsive disorder (OCD) and other anxiety disorders treated with SSRIs with an increased risk of suicide.

Physicians who consider prescribing these medications must remember that the drugs are not currently approved for the treatment of panic disorder in the pediatric and adolescent (< 18 y) population. Therefore, they must balance the risks of suicidal ideation with the medications' potential benefits, as demonstrated in adults. Once the patient starts therapy, the physician, parents, and caregivers must closely monitor the patient for any signs of irritability, agitation, behavioral changes, and/or suicidality.{[1]

Diazepam (Valium)

Clinical Context:  Individualize the dosage of diazepam and increase it cautiously to avoid adverse effects. Note the need to use it for shortest time possible in patients when abrupt discontinuation is not a risk.

Furthermore, diazepam should not be continued if the patient is not also being monitored by a therapist on a regular basis.

Class Summary

These agents depress all levels of the central nervous system (eg, the limbic and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Several benzodiazepines have been used in children for a variety of indications, including reduction of anticipatory or acute situational anxiety. Note the importance of caution and use only in conjunction with psychotherapy aimed at reducing the patient's time using benzodiazepines.

Many pediatricians are most familiar with diazepam (Valium), and no particular reason exists to prefer another benzodiazepine in children because diazepam is available as a generic preparation and has a smooth, longer action that may be advantageous.

Lorazepam (Ativan) has the advantage of being quite short acting in the event of disinhibition, but it is not as useful for treatment of panic disorder because of the frequent dosing.

Clonazepam (Klonopin) has been studied in panic disorder but has been noted anecdotally to have some increased risk of behavioral disinhibition.

Author

Jeffrey S Forrest, MD, Staff Psychiatrist, Orange County Health Care Agency

Disclosure: Nothing to disclose.

Coauthor(s)

Nirupama Natarajan, MD, Fellow in Child and Adolescent Psychiatry, Carilion Clinic, Virginia Tech Carilion School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Caroly Pataki, MD, Health Sciences Clinical Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Chet Johnson, MD Medical Director, Child Development Unit, Department of Pediatrics, Professor, University of Kansas Medical Center

Chet Johnson, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Lene Holm Larsen, PhD Instructor, Department of Child and Adolescent Psychiatry, Children's Memorial Hospital of Chicago

Disclosure: Nothing to disclose.

Carrie Sylvester, MD, MPH Senior Child and Adolescent Psychiatrist, Sound Mental Health

Carrie Sylvester, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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