Pharmacotherapy for anxiety disorders in children and adolescents

Agent	Initial daily dose	Suggested dose titration based upon response	Maintenance daily dose range	Selected characteristics*^¶
Selective serotonin reuptake inhibitors (SSRIs)*
Fluoxetine	Children: 5 to 10 mg Adolescents: 10 mg	After 7 days increase daily dose to 20 mg; then after 4 and 8 weeks increase daily dose by 20 mg, if needed	10 to 80 mg	Prolonged half-life (ie, approximately 5 days). Inhibits CYP2D6 and CYP2C19.
Fluvoxamine	25 to 50 mg at bedtime	Increase daily dose by 25 mg (child) or 25 to 50 mg (adolescent) after a minimum of 7 days, if needed	50 to 300 mg	Girls generally require lower maintenance doses than boys. Give with meals and bedtime in divided doses to minimize side effects. Inhibits CYP1A2 and 2C19.
Sertraline	12.5 to 25 mg	Increase daily dose by 12.5 mg (child) or 25 to 50 mg (adolescent) after a minimum of 7 days, if needed	50 to 200 mg	Diarrhea more frequent than other SSRIs. Metabolized by CYP3A4.
Escitalopram	10 mg	Increase daily dose by 5 to 10 mg after a minimum of 14 days, if needed	10 to 20 mg	Short half-life. Metabolized by CYP2C19. Prolongation of QT interval.
Paroxetine	5 to 10 mg	Increase daily dose by 5 mg (child) or 10 mg (adolescent) after a minimum of 7 days, if needed	10 to 60 mg	Short half-life. More suicidality than other SSRIs. Mild anticholinergic side effects. Metabolized by and inhibits CYP2D6. Weight gain.
Serotonin norepinephrine reuptake inhibitor (SNRI)*
Venlafaxine extended-release (ER)	37.5 mg	Increase daily dose by 37.5 mg (child) or 75 mg (adolescent) after a minimum of 7 days, if needed	75 to 225 mg	More suicidality and less efficacious than SSRIs. Dose-related increase in diastolic blood pressure and/or heart rate may be seen. Some children may experience weight loss. Prolongation of QT interval.
Duloxetine	30 mg	Increase daily dose by 30 mg after a minimum of 14 days, if needed	30 to 60 mg Some patients may benefit from a higher daily dose, increased by 30 mg increments every 2 to 4 weeks, to maximum of 120 mg per day	More suicidality and less efficacious than SSRIs. Some children may experience dose-related gastrointestinal-related adverse effects (eg, nausea and abdominal pain), and weight loss. Palpitations and increased pulse were observed more frequently than with placebo in a pediatric GAD trial. Metabolized by CYP1A2 and CYP2D6. Inhibits CYP2D6.
Tricyclic antidepressants (TCA)
Clomipramine	Children ≥10 years old and adolescents: 25 mg	Increase daily dose by 25 mg after a minimum of 7 days, if needed; give in divided doses with meals and bedtime	25 to 250 mg (2 to 6^Δ mg/kg per day); doses >2.5 mg/kg per day should be used cautiously^Δ	Applies to clomipramine and imipramine: Cardiovascular screening including ECG recommended prior to initiating treatment.^Δ Anticholinergic side effects may limit usefulness in children. Drowsiness, irritability and vomiting may be seen. Give in divided doses with meals and at bedtime to minimize side effects. Metabolized by CYP1A2 and 2D6.
Imipramine	10 to 25 mg	Increase daily dose by 25 mg after a minimum of 7 days, if needed; give in divided doses with meals and bedtime	10 to 300 mg (2 to 6^Δ mg/kg per day); doses >2.5 mg/kg per day should be used cautiously^Δ
Benzodiazepines
Clonazepam	0.25 to 0.5 mg		1 to 6 mg	Applies to clonazepam and lorazepam: Drowsiness, irritability, and oppositional behavior may be seen. Subject to abuse, addiction and diversion.
Lorazepam	0.25 to 0.5 mg		0.25 to 8 mg

Clinicians should be aware of the potential for activating side effects of antidepressants in younger children and regulatory warnings of potential for an increased risk of suicidality in children. With the exception of duloxetine and escitalopram, antidepressants are not approved by the US Food & Drug Administration for treatment of anxiety disorders in children. Recommended doses are those shown to have been effective in randomized controlled trials of children with various anxiety disorders and clinical experience. All doses shown are for oral administration. Obsessive-compulsive disorder (OCD) is reviewed separately in UpToDate.

CYP: cytochrome P450 drug metabolizing enzymes; ECG: electrocardiogram; GAD: generalized anxiety disorder.

* Common generally mild adverse effects of SSRIs and SNRIs seen in children treated for anxiety disorders may include headache, anorexia, vomiting, sleep disturbance and somnolence.

¶ This table notes when agents are moderate or strong inhibitors of CYP isoenzymes; significant interactions can occasionally occur due to weak inhibition of CYP isoenzymes (eg, target drug is highly dependent on CYP metabolism and has a narrow therapeutic index). This table also notes major CYP isoenzymes involved in metabolism of these agents, but other CYP isoenzymes may also contribute. Accordingly, specific interactions should be checked using a drug interactions program such as the Lexicomp drug interactions program included with UpToDate.

Δ Dose-related ECG changes have been reported in children and close monitoring is necessary with larger doses. According to the product information approved in the United States, doses >2.5 mg/kg per day are not recommended in children.

Courtesy of authors with additional data from:

Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 2014; 14 Suppl 1:S1.
Rynn M, Puliafico A, Heleniak C, et al. Advances in pharmacotherapy for pediatric anxiety disorders. Depress Anxiety 2011; 28:76.
Martin A, Scahill L, Kratochvil C. Pediatric Psychopharmacology, Oxford University Press, New York 2010. p.480.

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Pharmacotherapy for anxiety disorders in children and adolescents