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Introduction
Background
Generalized anxiety disorder (GAD) is associated with persistent, excessive, and unrealistic worry that is not focused on a specific object or situation. It was introduced in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),1 replacing overanxious disorder of childhood (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition [DSM-III-R]).2, 3 (See History.) Children with GAD worry more often and more intensely than other children in the same circumstances. They may worry excessively about their performance and competence at school or in sporting events, about personal safety and the safety of family members, or about natural disasters and future events. The focus of worry may shift, but the inability to control the worry persists. Because children with GAD have a hard time "turning off" the worrying, their ability to concentrate, process information, and engage successfully in various activities may be impaired. In addition, problems with insecurity that often result in frequent seeking of reassurance may interfere with their personal growth and social relationships. Further,
children with GAD often seem overly conforming, perfectionistic, and self-critical. They may insist on redoing even fairly insignificant tasks several times to get them "just right." This excessive structuring of one's life is used as a defense against the generalized anxiety related to the concern about the individual's overall and specific performance. (See Treatment.) Little empiric data are available regarding the physiologic indicators of anxiety in children. 4 The high cost, lack of normative data, idiosyncratic patterns, and high sensitivity of cardiovascular and electrodermal measures in children contribute to the difficulties in physiologic assessment of anxiety in children. 5 (See Differentials.) Go to Pediatric Obsessive-Compulsive Disorder, Pediatric Panic Disorder, and Anxiety Disorders for complete information on these topics. Complications Potential complications of GAD include the following (see Prognosis): Comorbid depression and other comorbid conditions School truancy and withdrawal from other age-appropriate activities Strained family relationships when the child's anxiety contributes to irritability, noncompliance, demanding behavior, and/or chronic reassurance seeking "Self-medication" leading to substance abuse by adolescents Parents' inability to help in the child's treatment or to model adaptive coping/anxiety management because of their own untreated anxiety (or other psychiatric condition)
Etiology
Multiple factors are thought to contribute to the development of generalized anxiety disorder (GAD) and to the broad category of anxiety disorders. Biologic, familial, and environmental factors are considered important. Behavioral inhibition, an early temperament associated with aversion to novel situations, has been found to be associated with later development of anxiety disorders. Research has demonstrated an association between parents with anxiety disorders and children with behavioral inhibition. The tendency of anxiety to occur in families also has been established. Anxious parents may genetically predispose their children to anxiety, model anxious behavior, and behave and/or parent in ways that encourage and maintain anxious behavior in the child. Environmental factors, such as other parental emotional problems, disrupted attachment, stressful life events, and traumatic experiences, also may place the child at risk for developing GAD. The role of the family in understanding child anxiety is important, particularly in situations in which the needs of younger children who are developmentally limited in their ability to benefit from direct individual intervention are considered.
Pathophysiology Epidemiology
Incidence in the United States The prevalence of generalized anxiety disorder (GAD) in children and adolescents ranges from 2.9-4.6%.
International incidence The worldwide prevalence of GAD is unknown. Race predilection Specific racial or cultural group prevalence rates are not available. Sex predilection In childhood, the sex distribution tends to be equal for females and males. In adolescence, a female-to-male ratio of 6:1 has been suggested; however, epidemiologic study results vary. Age predilection The age of onset varies, but GAD is more common in adolescents and older children than in young children. In addition, affected adolescents and older children tend to have more symptoms than do affected younger children.
Prognosis
The prognosis is thought to be relatively good when treatment is implemented early and effectively. However, the child remains at risk for developing generalized anxiety disorder (GAD) or other anxiety disorders. For example, Last and colleagues reported an 80% recovery rate from overanxious disorder during a 3- to 4-year follow-up period. However, 35% of the children developed a new psychiatric disorder in the same interval.6 Mortality and morbidity Anxiety disorders have a high rate of comorbidity. Children with GAD are also likely to meet criteria for other anxiety disorders and, to a lesser degree, for a depressive or disruptive behavior disorder. Deaths related to GAD in childhood and adolescence are related more to comorbid conditions, such as depression, than to GAD. Children and adolescents with both depression and an anxiety disorder tend to have more severe forms of depression; therefore, GAD should be viewed as a risk factor for morbidity and mortality. Anxiety disorders tend to be unstable over time. That is, a child may struggle with anxiety for a long period, but it may not necessarily be a result of the same specific anxiety disorder. Anxiety is a serious problem in children and adolescents. We now understand that, in addition to deleteriously affecting the child's social and academic functioning, anxiety can cause serious long-term consequences. Many children with one of the anxiety disorders suffer intermittently for the rest of their lives. Other serious psychiatric conditions, such as major depressive disorder and substance misuse, are closely associated with pediatric anxiety if not treated in a timely and effective manner. GAD also may co-occur with conditions associated with stress, such as irritable bowel syndrome and headaches. The long-term physiologic effects of stress are more likely to cause nonpsychiatric gastrointestinal, cardiovascular, or other sequelae later in life.
Patient Education
Psychoeducation should be part of the treatment process. Patients and parents should have a good understanding of the contributing and maintaining factors of anxiety. Also, they should be clear regarding treatment goals, processes, and expectations. For patient education information, see the Anxiety Center, as well as Anxiety, Panic Attacks, and Hyperventilation.
Clinical
History
Children with generalized anxiety disorder (GAD) may experience somatic symptoms such as shortness of breath, rapid heartbeat, sweating, nausea or diarrhea, frequent urination, cold and clammy hands, dry mouth, trouble swallowing, or a "lump in the throat." Problems with muscle tension also can occur, including trembling, twitching, a shaky feeling, and muscle soreness or aches. Patients often complain of stomachaches and headaches. Despite these symptoms, few findings are noted on physical examination. An evaluation for generalized anxiety disorder (GAD) should include data gathering through diagnostic interviews with the child and parent, direct observation, and questionnaires. Family history of anxiety and mood disorders, the child's early temperament and adjustment to school, and life stressors or disruptions are among important factors to consider in GAD. Structured interviews yielding DSM-IV diagnoses, such as the Diagnostic Interview Schedule for Children (DISC) and 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),7 and the Screen for Child Anxiety Related Emotional Disorders (SCARED) child and parent versions, can be used to further assess anxiety symptoms. The DSM-IV requires the following to satisfy a diagnosis of GAD: Excessive anxiety and worry, occurring more days than not for at least 6 months, about a number of events or activities Difficulty controlling the worry One of the following symptoms in association with the worry: restlessness, fatigue, poor concentration, irritability, muscle tension, or sleep disturbance
Focus of worry that is not confined to features of another Axis I diagnosis, eg, worry about having a panic attack, social embarrassment, or separation from caregiver Clinically significant distress or impairment experienced in social, school, or other important areas Disturbance that is not due to a substance or general medical condition and that does not occur exclusively during a mood disorder, a psychotic disorder, or in association with a pervasive developmental disorder
Physical Examination
As previously mentioned, children with generalized anxiety disorder (GAD) may experience somatic symptoms, including shortness of breath, rapid heartbeat, sweating, nausea or diarrhea, frequent urination, cold and clammy hands, dry mouth, trouble swallowing, or a "lump in the throat." Problems with muscle tension, such as trembling, twitching, a shaky feeling, and muscle soreness or aches, may also occur, and patients often complain of stomachaches and headaches. Despite these symptoms, few findings are noted on physical examination.
Causes
Differentials
Anxiety Disorder: Panic Disorder Anxiety Disorder: Separation Anxiety and School Refusal Attention Deficit Hyperactivity Disorder Child Abuse & Neglect: Posttraumatic Stress Disorder Eating Disorder: Anorexia Hyperthyroidism Hypothyroidism Mood Disorder: Bipolar Disorder Pediatric Obsessive-Compulsive Disorder Thyroiditis
Diagnostic Considerations
Substance-induced anxiety disorder, anxiety disorder due to a general medical condition, an adjustment disorder, or psychotic disorder also should be considered. Distinguishing anxiety from developmentally appropriate fears is important. Throughout childhood and early adolescence, children experience various transitory fears occurring concurrently with their ability to recognize and understand potential dangers in their environment. A progression occurs from immediate, tangible fears (eg, separation from caregiver, strangers) to anticipatory, less tangible fears (eg, bad dreams, getting hurt, school failure). Children are expected to overcome and resolve these fears as part of the developmental process. Distinguishing anxiety from realistic worry is also imperative. Worry can be thought of as a feeling of unease or concern about something. It represents an internal representation of a realistic threat. For example, a child with a learning disability may worry about an upcoming examination, or a child with a medical condition may worry about an upcoming surgery. This kind of worry is expected to be specific to a situation, and it is expected to subside once the situation has passed. Thus, the temporal requirement for generalized anxiety disorder (GAD) diagnosis (6 mo) is not met. Conditions to consider in the differential diagnosis of GAD, in addition to those in the next section, include the following:
Oppositional defiant disorder Peptic ulcer disease Avoidant personality Hypochondriasis Social phobia and selective mutism Specific phobia Trichotillomania Asthma Depression Dysthymic disorder Obstructive sleep apnea syndrome Somatization
Go to Pediatric Obsessive-Compulsive Disorder, Pediatric Panic Disorder, and Anxiety Disorders for complete information on these topics.
Workup
Approach Considerations
Consider urine drug screening, thyroid-stimulating hormone level assessment, and less common laboratory tests based on history and physical findings. Excessive laboratory exclusion of somatic complaints is to be avoided; however, careful interview and physical examination assessment of stress-related symptoms should be repeated if the psychological diagnostic picture is unclear.
Treatment
Approach Considerations
For patients for whom medication is prescribed, regular appointments with a child and adolescent psychiatrist or developmental-behavioral pediatrician are necessary for the duration of treatment. Parents and patients must be warned of the possible risks of activation and disinhibition and what to do in such circumstances. Go to Pediatric Obsessive-Compulsive Disorder, Pediatric Panic Disorder, and Anxiety Disorders for complete information on these topics.
Patient therapy Weekly outpatient therapy for 3-4 months with less frequent follow-up booster sessions may be sufficient. A cognitive-behavioral approach is likely to be most beneficial. Treatment should consist of individual sessions with family involvement to support the treatment process. Cognitive therapy features may be incorporated into an eclectic approach by highly skilled and experienced therapists. Psychodynamic therapies, including play therapy, are time-honored modalities, but most outcomes research has focused on the brief or intermediate therapies, which are more structured.
Ginsburg conducted a study to determine the effectiveness of preventive intervention in the prevention and/or amelioration of anxiety symptoms in children of parents with anxiety disorders and found evidence to support the concept that family-based intervention may yield benefits in children at risk for anxiety. 15 Forty children and their families were randomized to undergo an 8-week cognitive-behavioral intervention (the Coping and Promoting Strength [CAPS] program; 20 participants) or a wait list control condition (20 participants). After a 1-year follow-up, none of the children in the CAPS program developed an anxiety disorder, while 30% of the children in the wait list group did. The authors of one study developed a novel prediagnosis intervention, Strongest Families, which includes trained nonprofessionals supervised by mental health professionals for children with disruptive behavior and/or anxiety disorders. The intervention provides care using a handbook, instructional videos, and weekly telephone contacts. The study results noted that these telephone-based treatments resulted in a significant decrease in the proportion of children diagnosed with disruptive behavior or anxiety disorders; this treatment may be an option for those patients who are unable to attend face-to-face sessions.16
Referrals
Early referral to a psychologist, psychiatrist, or behavioral-developmental pediatrician for evaluation and treatment can alleviate symptoms and stress that may be the early manifestations of a more severe disorder. Family therapy referral also may be indicated, but that may be best managed by the mental health professional or the developmental and behavioral pediatrician who performs the consultative evaluation.
Medication
Medication is ideally adjunctive to psychological treatment of generalized anxiety disorder (GAD). Unfortunately, lack of experienced and qualified therapists may preclude an adequate trial of cognitivebehavioral therapy. Selective serotonin reuptake inhibitor (SSRI) antidepressants are currently first-line medications in the pharmacotherapy of anxiety disorders in children. These antidepressants are powerful anxiolytics with a broader spectrum that may improve comorbid affective disorders and symptoms of anxiety. Benzodiazepines have a relatively favorable adverse effect profile but are generally not chosen as first-line treatments for anxiety in children and adolescents. These agents may cause behavioral disinhibition in young children. They also have street value as drugs of abuse. Buspirone (BuSpar) is an anxiolytic agent whose efficacy in the treatment of anxiety disorders in children and adolescents has not yet been demonstrated. BuSpar is slow to work in adults but does not cause habituation or disinhibition. Antihistamines and antipsychotics are not recommended for treatment of childhood-onset anxiety disorders. Pregabalin (Lyrica), an anticonvulsant, has been approved for use in adults by the European Commission (EC) and the US Food and Drug Administration (FDA) for the management of diabetic peripheral neuropathy, postherpetic neuralgia, and adjunctive treatment of partial-onset seizures. On March 27, 2006, the EC approved a new indication for pregabalin, allowing its use in adults for the treatment of GAD in the European Union.
Pregabalin is not FDA approved for treating adult or pediatric GAD in the United States. EC approval was based on a review of data from 5 randomized, double-blind clinical trials in more than 2000 patients, which showed that pregabalin provided rapid and sustained efficacy in treating GAD, yielding significant relief from psychic and somatic symptoms within the first week of treatment. Most adverse events were mild to moderate in intensity and generally dose-related. Dizziness and drowsiness were most frequently reported. Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. It binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, pregabalin reduces the calciumdependent release of several neurotransmitters, possibly by modulating calcium channel function. Pregabalin is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
now available in generic preparations. The drugs long half-life is an advantage and a drawback. If fluoxetine works well, an occasional missed dose is not a problem; if problems occur, eliminating all active metabolites takes a long time. Adverse effects of SSRIs seem to be quite idiosyncratic; thus, relatively few reasons exist to prefer one to another at this point if dosing is started at a conservative level and advanced as tolerated. Adult Dose 5 mg/d PO initially; may advance by 5-mg increments q3-5d to 20 mg/d Then, advance in this manner again after about 6 wk; for GAD, higher doses commonly used for other anxiety disorders or depressive disorders usually are not required <18 years: Not approved 2 mg/d in young children or extremely anxious adolescents initially; may benefit from doses of 5-10 mg/d; rate of dosage advance should be more conservative than in adults Fluvoxamine (Luvox CR) 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. Adult Dose 50 mg PO qhs initially as single dose, increase dose in 50-mg increments q4-7d as tolerated until maximum therapeutic benefit achieved; divide total daily dose into 2 doses; if doses are unequal, administer larger dose hs; not to exceed 300 mg/d <8 years: Not established 8-17 years: 25 mg PO qhs initially as single dose, increase dose in 25-mg increments q4-7d as tolerated until maximum therapeutic benefit achieved, divide total daily doses higher than 50 mg into 2 doses; if doses are unequal, administer larger dose hs Females children may respond to lower doses Age up to 11 years: Not to exceed 200 mg daily Adolescents may require higher doses up to adult maximum of 300 mg daily Sertraline (Zoloft) Zoloft selectively inhibits presynaptic serotonin reuptake. 50 mg PO qd; if needed, may titrate upward by 50-mg/d increments q7d; not to exceed 200 mg/d <6 years: Not established 6-12 years: 25 mg PO qd initially; if inadequate response, may increase gradually at intervals of at least 1 wk; not to exceed 200 mg daily 13-17 years: 50 mg PO qd initially; if inadequate response, may increase gradually at intervals of at least 1wk; not to exceed 200 mg daily Paroxetine (Paxil, Pexeva) This is unlabeled use. Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and
Pediatric Dose
Drug Name
Description
Pediatric Dose
Pediatric Dose
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. Initial therapy: Start with 10 mg/d PO and increase in 10 mg/d increments, if necessary Adult Dose Dose changes should occur at intervals of at least 1 wk; usual dose range is 10-80 mg/d; not to exceed 80 mg/d Pediatric Dose <18 years: Not established >18 years: Administer as in adults
Description
This is a 5-HT1 agonist with serotonergic neurotransmission and some dopaminergic effects in the CNS. Buspirone hydrochloride has an anxiolytic effect, but it may take up to 2-3 wk to reach full efficacy. A relative disadvantage to the administration of this drug is a lack of official approval for its use in individuals under age 18 years. 15 mg/d PO divided tid initially; may increase by 5 mg/d q2-4d; not to exceed 60 mg/d <18 years: Not approved; not established; suggested dose based on limited data Children: 2.5 mg/d PO; may increase by 2.5 mg q3-4d, adding doses to achieve tid dosing with a total daily dose of 20 mg/d Adolescents: Titrate as for children with eventual adult dose Note that younger individuals and developmentally delayed individuals may respond to lower doses than adults, thus conservative advancing is prudent
Adult Dose
Pediatric Dose
Follow-up
Further Inpatient Care Further Outpatient Care In/Out Patient Meds Transfer Deterrence/Prevention Complications Prognosis Patient Education
Miscellaneous
Medical/Legal Pitfalls Special Concerns
Test Questions
Question 1:
A 10-year-old boy is having difficulty completing his homework and is having many arguments with his mother about this issue. She reports that he repeatedly works on a small part of the homework and complains that it is not perfect enough, so he never moves on to the other work. She says that he has had very good grades but always compares himself with his older sister, who is an A student. Lately, he also has been complaining of stomachaches and asking to remain home from school. Which of the following should be the next step? A. B. C. D. E. Order an imaging study of his upper gastrointestinal tract. Talk with the mother about sibling rivalry issues. Tell her that this is classic school phobia and that he simply needs to be sent to school. Refer them to a child psychologist, psychiatrist, behavioral developmental pediatrician, or other mental health professional for evaluation and possible treatment. Refer them to a social worker or counselor for therapy since this is clearly simple anxiety.
The correct answer is D: This case actually has somewhat of a broad differential diagnosis within the spectrum of anxiety and depressive disorders. Many experienced social workers may make a correct diagnosis and provide competent therapy, but it is important to know that the patient and parent are referred to an individual who can provide comprehensive evaluation and treatment. The management of generalized anxiety disorder, obsessive-compulsive disorder, a depressive disorder, a subtle learning disorder in a child who had succeeded to that point, and a variety of family factors or other life stressors may be needed and is best performed by trained mental health professionals.
Question 2: A 12-year-old girl is undergoing a sports physical. She confides that she is very worried about participating this year because, at times, she has had to wait alone after dark to be picked up after practice. Her mother separately states that her daughter has seemed very nervous about school activities this year and wonders about a mental health referral. Which of the following should be the next step? A. B. C. D. E. Compliment the mother on her astute observation, and refer them to a social worker, psychologist, or psychiatrist. Explore how truly dangerous the environment is and what other worries the child might have before discussing an alternative plan with the girl and her mother together. Offer the girl a prescription for an antianxiety medication so that she will not worry so much and will enjoy her activities. Tell the mother that it is better that the girl take a year off from the activities as she will grow out of her fearfulness in due time. Assure the girl that lots of children have these concerns and that it is simply normal worry.
The correct answer is B: This is most likely normal worry, but the circumstance warrants some examination. Few situations exist in which a child or young adolescent safely can wait after dark, especially in an urban area. If the child has been stressed by this kind of situation, she may be generalizing her fears. Also important is getting some idea of why she is being left without alienating the parent or causing difficulty between the girl and her mother.
Question 1 (T/F): Generalized anxiety disorder is more common in prepubertal girls than in prepubertal boys.
The correct answer is False: Generalized anxiety disorder is observed equally in boys and girls until puberty, when the female-to-male ratio gradually rises to 6:1.
Question 2 (T/F): Generalized anxiety disorder tends to be familial. The correct answer is True: The cause for the familial nature of the disorder may be a combination of genetic temperament, modeling of anxious behavior, or other aspects of parenting style.
Question 3 (T/F): Fluoxetine (Prozac) is the drug of choice for generalized anxiety disorder. The correct answer is False: Fluoxetine is a good choice because of its availability in generic form, long use in children and adolescents, and efficacy in comorbid depression. However, little reason exists to prefer one selective serotonin reuptake inhibitor over another. Further, advantages may exist in using a benzodiazepine in some children with pure anxiety who need rapid relief for a relatively short duration while engaging in therapy.
Question 4 (T/F): Cognitive-behavioral therapy with family involvement is the currently recommended psychotherapy of choice for children with generalized anxiety disorder. The correct answer is True: Family involvement is essential for treatment of children with anxiety. Cognitive therapy features may be incorporated into an eclectic approach by highly skilled and experienced therapists. Psychodynamic therapies, including play therapy, are time-honored modalities, but most outcomes research has focused on the brief or intermediate more structured therapies.
7. March JS, Parker JD, Sullivan K, Stallings P, Conners CK. The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity. J Am Acad Child Adolesc Psychiatry. Apr 1997;36(4):554-65. [Medline]. 8. Kendall PC, Chu BC, Pimental SS. Treating anxiety disorders in youth. In: Kendall PC, ed. Child & Adolescent Therapy: Cognitive-Behavioral Procedures. 2nd ed. New York, NY: Guilford; 2000:235-87. 9. Walkup JT, Albano AM, Piacentini J, Birmaher B, Compton SN, Sherrill JT, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. Dec 25 2008;359(26):275366. [Medline]. [Full Text]. 10. Barrett PM, Dadds MR, Rapee RM. Family treatment of childhood anxiety: a controlled trial. J Consult Clin Psychol. Apr 1996;64(2):333-42. [Medline]. 11. Last CG, Hansen C, Franco N. Cognitive-behavioral treatment of school phobia. J Am Acad Child Adolesc Psychiatry. Apr 1998;37(4):404-11. [Medline]. 12. Silverman WK, Kurtines WM, Ginsburg GS, Weems CF, Lumpkin PW, Carmichael DH. Treating anxiety disorders in children with group cognitive-behaviorial therapy: a randomized clinical trial. J Consult Clin Psychol. Dec 1999;67(6):995-1003. [Medline]. 13. Spence S. Helping Your Anxious Child: A Step-By-Step Guide for Parents. Oakland, Calif: New Harbinger Publications; 2000. 14. Manassis K. Keys to Parenting Your Anxious Child. Hauppage, NY: Barron's Educational Series; 1996. 15. {Best Evidence} Ginsburg GS. The Child Anxiety Prevention Study: intervention model and primary outcomes. J Consult Clin Psychol. Jun 2009;77(3):580-7. [Medline]. 16. McGrath PJ, Lingley-Pottie P, Thurston C, et al. Telephone-based mental health interventions for child disruptive behavior or anxiety disorders: randomized trials and overall analysis. J Am Acad Child Adolesc Psychiatry. Nov 2011;50(11):1162-72. [Medline]. 17. Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment. Am J Psychiatry. Jan 2006;163(1):41-7. [Medline].
Acknowledgments
eMedicine GPS2 Authoring System Article Content Generated: 02/02/12 02:16:45 PM by Nutter, Dennis A