Anxiety Disorders in Children and Adolescents: Pharmacotherapy

By | July 1, 2012

With advances in the identification of child- and adolescent-onset anxiety () has come a concomitant increase in the application of pharmacological treatments borrowed in part from successful strategies applied in adult populations with similar disorders (). Conversely, although psychopharmacological interventions are increasingly recognized as an essential part of the treatment armamentarium for anxious youths (), the exact place of medication strategies alone and in combination with psychosocial interventions is as yet unclear (American Academy of Child and Adolescent Psychiatry). Outside of obsessive-compulsive disorder (), few empirical studies of the efficacy, much less the safety, of specific medications have been conducted (), with the use of many compounds in the pediatric population supported solely by clinical lore (). In particular, most of the reported investigations either have been open trials or have been conducted in patient populations that are not well characterized (), making it difficult to determine whether these medications would be effective in typical clinical populations (1998).

Table Approach to prescribing psychotropic medication

Conduct a comprehensive baseline evaluation, including rating scales and, if indicated, laboratory measures.
Carefully consider the question of differential therapeutics to identity potential targets for medication treatment as distinct from psychosocial treatments when possible.
Establish risk-benefit ratios for each treatment, and obtain informed consent.
In general, begin with least complicated and risky drug strategies.
Define indicators for each important outcome domain to better track potential benefits and side effects.
Insofar as possible, use only one medication at a time to minimize confusion with respect to tracking outcome.
When adjusting medications, be sure to consider both dose-response (intensity) and time-response (temporal) characteristics of the chosen medication in relation to the patient’s psychiatric disorder.
Use an evidence-based stages of treatment model, and establish a defined end point at which a decision can be made about whether the expected benefit has occurred and whether additional treatment(s) can or should be implemented.

In lieu of a detailed review of psychopharmacology for pediatric anxiety disorders, which is beyond the scope of this chapter (), Table Approach to prescribing psychotropic medication summarizes the general approach to prescribing medication for anxious youth, and Table Commonly used medications inventories the drugs most commonly used for this purpose. Given the absence of solid empirical data to guide the ordering of treatments, most clinicians treating anxiety in children and adolescents will (or at least should) begin with cognitive-behavioral therapy, which has considerably more empirical support (), and advance to a pharmacological intervention only if the patient does not rapidly respond to cognitive-behavioral therapy. Factors leading to early medication intervention might include unavailability of cognitive-behavioral therapy, patient preference, and severe or multiple comorbidity or suicidality. For many patients with moderately severe to severe symptoms, the combination of cognitive-behavioral therapy and medication may be most likely to lead to durable symptom remission, although empirical evidence for this assertion is largely lacking ().

Other complexities are present when using psychotropic medication in pediatric patients that are not present with most adults. For example, children less commonly seek treatment themselves. Alternatively, parents are sometimes “cornered into treatment” by pressure from school or social service agencies. Children commonly fear being labeled a “mental patient” by peers or extended family, so exploring the meaning of the medication to the child is important. Parenthetically, however, prescribing medication in a medical context, namely for an illness that is bothering the child and from which he or she wants relief, increases compliance. The form and taste of medication as well as route of administration influence compliance, especially in younger children. If the cost of the drug is prohibitive, or it is not available locally, treatment may be interrupted. Although many methods are available to assess compliance, such as direct monitoring, questionnaires, pill counts, and measuring levels in body fluids, none is completely reliable. A good therapeutic alliance, a careful explanation of benefits and risks coupled with written informed consent, a combination of medication with targeted psychosocial therapies, and thoughtful monitoring are the factors most likely to result in a positive outcome. Friendly and collegial communication with pediatricians, family doctors, and other professionals involved in the child’s care also enhances compliance. Similarly, patients and their families must be informed that not all medicines help everybody and that a period of medication trial and error may be necessary to find the medication that is most helpful.

Table Commonly used medications

Psychotropic class Drug Brand name Therapeutic applications Comments
Serotonin reuptake inhibitors (SRIs) Citalopram Celexa Serotonin reuptake inhibitors may be useful in all anxiety disorders except specific phobia. SRIs are first-line compounds, with broad-spectrum activity in many mood and anxiety disorders and unique activity in obsessive-compulsive disorder; well tolerated compared with traditional tricyclic antidepressants.
Fluoxetine Prozac
Fluvoxamine Luvox
Paroxetine Paxil
Sertraline Zoloft
Tricyclic antidepressants (TCAs) Imipramine Tofranil All anxiety disorders except OCD and specific phobia Second-line drugs after the SRIs; require ECG and laboratory monitoring; probably not effective in depression.
Nortriptyline Pamelor
Desipramine Norpramin
Clomipramine Anafranil Only tricyclic antidepressant used for OCD Use after two to three failed SRI trials.
Benzodiazepines Alprazolam Xanax Situation and anticipatory anxiety across all anxiety disorders Best for short-term use while waiting for an serotonin reuptake inhibitor to “kick in.” Disinhibition and physiological dependence may be problematic.
Clonazepam Klonopin
Lorazepam Ativan
Other drugs Buspirone BuSpar Generalized anxiety disorder

Specific social phobia

Buspirone is broadly anxiolytic; it is not effective in panic disorder with agoraphobia or OCD; may be useful in place of a benzodiazepine when substance abuse is an issue. Propranolol and other β-blockers are useful primarily in acute performance anxiety.
Propranolol Inderal

When patients’ symptoms do not respond or only partially respond to initial pharmacotherapy, the clinician must reassess whether treatment targets have been appropriately identified and whether treatments have been appropriately implemented. Conversely, increasing the intensity of the treatment — for example, by adding behavioral family therapy, increasing the dose of medication, or changing medication — may be necessary (). Rarely, patients will benefit from combination medication regimens () (e.g., a serotonin reuptake inhibitor with an antipsychotic such as risperidone) when comorbid schizotypal personality disorder or a tic spectrum disorder is present in the patient with a primary diagnosis of obsessive-compulsive disorder (). In many cases, partial improvement is all that can be expected; distinguishing between improvement and residual impairment in the context of the natural history of the disorder is an important part of differential therapeutics and of the psychoeducational process.

To date, the available data suggest that high-potency benzodiazepines may be appropriate short-term treatments for a broad range of anticipatory and situation-related anxiety symptoms. Although empirical data are more limited outside of obsessive-compulsive disorder, for which they are robust, the selective serotonin re-uptake inhibitors are probably the agents of choice when long-term treatment is anticipated. Buspirone is a potentially useful agent in generalized anxiety disorder, and its relatively benign side-effect profile and low abuse potential make it an attractive choice, particularly in an adolescent population at risk for substance abuse. Targeted propranolol may be useful to treat performance anxiety in patients with nongeneralized social phobia. Tricyclic antidepressants and antipsychotics should be avoided when possible because of their lack of demonstrated efficacy and high potential for serious side effects. Other agents have a smaller role, if any, to play; combinations of various compounds may be useful in treatment-resistant patients. In every patient, careful attention to dose-response relationships (the intensity dimension) and time-action effects (the temporal dimension) is critical to maximize benefit and minimize side effects.