eMedicine Specialties > Pediatrics: Developmental and Behavioral > Medical Topics
Anxiety Disorder: Generalized Anxiety: Treatment & Medication
Updated: Sep 18, 2006
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Behavioral and cognitive-behavioral therapies are among the most researched and promising treatments for childhood anxieties. Behavioral techniques (eg, relaxation training, modeling, imagining and visualizing, in vivo exposure) and cognitive techniques (eg, identifying and modifying self-talk, challenging irrational beliefs) often are used in combination with psychoeducation and contingency maintenance. Typically, children are taught to recognize early physiologic and cognitive signs of anxiety and to develop and implement coping techniques. The importance of parental participation in the treatment process recently has received attention. Adding a family component focused on techniques such as contingency management, communication, and problem solving to individual child cognitive-behavioral therapy has produced favorable long-term treatment benefits in several clinical trials (eg, Barrett, 1996; Last, 1998; Silverman, 1999).
For a more detailed review of current integrated cognitive-behavioral therapies for children with anxiety disorders, see Kendall et al (2000). Practically speaking, less successful real-world treatments are frequently encountered because of a dearth of qualified child therapists and a failure to recognize the importance of directly or indirectly (family component) treating parental anxiety. Several cognitive-behavioral therapy books, such as Helping Your Anxious Child: A Step-By-Step Guide for Parents by Sue Spence and Keys to Parenting Your Anxious Child (Barron's Parenting Keys) by Katharina Manassis, MD, are readily available for parents and their children to work with at home and at school.
Surgical Care
Children with an anxiety disorder are particularly likely to benefit from age-appropriate preoperative preparation including relaxation practice for elective procedures.
Consultations
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.
Diet
Limiting caffeine intake is appropriate.
Activity
Regular exercise promotes a sense of well-being that is particularly beneficial in individuals with anxiety and mood disorders.
Medication
Medication is ideally adjunctive to psychological treatment of GAD. Unfortunately, lack of experienced and qualified therapists may preclude an adequate trial of cognitive-behavioral 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.
Selective serotonin reuptake inhibitors
Antidepressant agents chemically unrelated to the tricyclic, tetracyclic, or other available antidepressants. Inhibit neuronal reuptake of serotonin, thus potentiating serotonergic activity in the brain, with the regulation of hypervigilance and other aspects of anxiety. These changes also may have a weak effect on norepinephrine and dopamine neuronal reuptake. Fluoxetine is presented as the 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 cardiac 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.
In October 2003, the US Food and Drug Administration (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. 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.
Fluoxetine (Prozac)
Longest history of use in children and adolescents. Now available in generic preparations. Long half-life is both an advantage and a drawback. If it 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
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
Pediatric
<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
Increases toxicity of diazepam and trazodone by decreasing clearance; interacts with many drugs because of inhibition of CYP450, CYP2C9, CYP2C19, CYP2D6, and CYP3A4; also 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); discontinue other serotonergic agents at least 2 wk before beginning SSRIs
Documented hypersensitivity; MAOIs concurrently or within last 2 wk
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
May cause agitation in children and adolescents; may cause bipolar switch in vulnerable individuals (as with all antidepressants); use with caution in individuals with compromised hepatic function or history of seizures; can cause movement problems, GI upset, weight change, and insomnia; anxious adults experience increased sensitivity to mild adverse effects
Caution with comorbid eating disorder, although is useful adjunct to treatment of eating disorders
Benzodiazepines
Depress all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Also increase the frequency of chlorine channel opening in response to GABA binding. GABA receptors are chlorine channels that mediate postsynaptic inhibition, resulting in postsynaptic neuron hyperpolarization. The final result is a sedative-hypnotic and anxiolytic effect.
Benzodiazepines have been used in children for a variety of indications, including the reduction of anticipatory or acute situational anxiety. Note the importance of using caution, and use only in conjunction with psychotherapy aimed at reducing the length of time on 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 GAD because of the frequent dosing. Clonazepam (Klonopin) has been studied in severe anxiety disorders but has been anecdotally (incorrectly) noted to have some increased risk of behavioral disinhibition. Alprazolam (Xanax) has been most studied in anxiety disorders in children.
Diazepam (Valium)
Individualize dosage, and increase cautiously to avoid adverse effects. Necessary to use for shortest time possible when abrupt discontinuation is not a risk. Further, should not be continued if patient discontinues psychotherapy.
Adult
2-10 mg PO q3-4h, repeat q2-4h prn; not to exceed 30 mg in 8 h
Pediatric
Infants and young children: 0.1-0.3 mg/kg/d PO
Older children and adolescents: 1-2.5 mg PO tid/qid
Phenothiazines, barbiturates, alcohol, and MAOIs increase CNS toxicity when administered concurrently
Documented hypersensitivity; narrow-angle glaucoma; pregnancy; avoid in individuals at risk of becoming pregnant
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)
Azaspirodecanediones
Buspirone is the anxiolytic in this category. It has high affinity for serotonin receptors, has a moderate affinity for dopamine receptors, and does not have cross-tolerance with benzodiazepines. No reports of dependence exist. One drawback is that it takes 1-4 weeks to become effective.
Buspirone hydrochloride (BuSpar)
5-HT1 agonist with serotonergic neurotransmission and some dopaminergic effects in CNS. Has anxiolytic effect but may take up to 2-3 wk for full efficacy. Relative disadvantage is lack of official approval for use in individuals <18 y.
Adult
15 mg/d PO divided tid initially; may increase by 5 mg/d q2-4d; not to exceed 60 mg/d
Pediatric
<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
Toxicity is increased with MAOIs, phenothiazines, and CNS depressants; increases toxicity of digoxin and haloperidol
Documented hypersensitivity; MAOIs concurrently or within last 2 wk
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in hepatic or renal impairment
Anticonvulsants
Pregabalin (Lyrica; Pfizer, Inc, New York, NY) 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 (Lyrica)
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.
Structural derivative of GABA. Mechanism of action is unknown. Binds with high affinity to alpha2 -delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Adult
50-100 mg PO bid
Pediatric
Not established
May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea upon abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min)
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| Overview: Anxiety Disorder: Generalized Anxiety |
| Differential Diagnoses & Workup: Anxiety Disorder: Generalized Anxiety |
 Treatment & Medication: Anxiety Disorder: Generalized Anxiety |
| Follow-up: Anxiety Disorder: Generalized Anxiety |
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References
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Further Reading
Keywords
anxiety disorder, generalized anxiety, overanxious disorder, overanxious reaction, generalized anxiety disorder of childhood, generalized anxiety disorder, GAD
