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.
Selective serotonin reuptake inhibitors
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]
Fluoxetine (Prozac)
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)
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)
Zoloft selectively inhibits presynaptic serotonin reuptake.
Paroxetine (Paxil, Pexeva)
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]
Benzodiazepines
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.
Diazepam (Valium)
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.
