Evidence-Based Reviews

An evidence-based approach to treating pediatric anxiety disorders

Current Psychiatry. 2012 September;11(9):16-21

References

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2. Beesdo K, Pine DS, Lieb R, et al. Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder. Arch Gen Psychiatry. 2010;67(1):47-57.

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4. Foley DL, Goldston DB, Costello EJ, et al. Proximal psychiatric risk factors for suicidality in youth: the Great Smoky Mountains Study. Arch Gen Psychiatry. 2006;63(9):1017-1024.

5. Jacobson CM, Muehlenkamp JJ, Miller AL, et al. Psychiatric impairment among adolescents engaging in different types of deliberate self-harm. J Clin Child Adolesc Psychol. 2008;37(2):363-375.

6. Ialongo N, Edelsohn G, Werthamer-Larsson L, et al. The significance of self-reported anxious symptoms in first-grade children. J Abnorm Child Psychol. 1994;22(4):441-455.

7. Pine DS, Cohen P, Gurley D, et al. The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry. 1998;55(1):56-64.

8. Rynn MA, Siqueland L, Rickels K. Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorders. Am J Psychiatry. 2001;158(12):2008-2014.

9. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008;359(26):2753-2766.

10. Maslowsky J, Mogg K, Bradley BP, et al. A preliminary investigation of neural correlates of treatment in adolescents with generalized anxiety disorder. J Child Adolesc Psychopharmacol. 2010;20(2):105-111.

11. Rynn MA, Riddle MA, Yeung PP, et al. Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials. Am J Psychiatry. 2007;164(2):290-300.

12. BuSpar [package insert] Princeton NJ: Bristol-Myers Squibb; 2010.

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14. Simeon JG, Ferguson HB, Knott V, et al. Clinical, cognitive, and neurophysiological effects of alprazolam in children and adolescents with overanxious and avoidant disorders. J Am Acad Child Adolesc Psychiatry. 1992;31(1):29-33.

15. Wagner KD, Berard R, Stein MB, et al. A multicenter, randomized, double-blind, placebo-controlled trial of paroxetine in children and adolescents with social anxiety disorder. Arch Gen Psychiatry. 2004;61(11):1153-1162.

16. March JS, Entusah AR, Rynn M, et al. A randomized controlled trial of venlafaxine ER versus placebo in pediatric social anxiety disorder. Biol Psychiatry. 2007;62(10):1149-1154.

17. Beidel DC, Turner SM, Sallee FR, et al. SET-C versus fluoxetine in the treatment of childhood social phobia. J Am Acad Child Adolesc Psychiatry. 2007;46(12):1622-1632.

18. Compton SN, Grant PJ, Chrisman AK, et al. Sertraline in children and adolescents with social anxiety disorder: an open trial. J Am Acad Child Adolesc Psychiatry. 2001;40(5):564-571.

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Panic disorder

Only 2 open-label studies of SSRIs have been conducted in pediatric patients with panic disorder. The first evaluated the effectiveness and tolerability of fluoxetine, sertraline, or paroxetine over 6 months in 12 patients; 67% no longer met criteria for panic disorder at endpoint.²¹ In this study, benzodiazepines—including clonazepam and lorazepam—were used in 67% of patients at the start of SSRI treatment. The authors suggested this strategy may be clinically useful for patients with panic disorder.

Clinical Point

Including a benzodiazepine at the start of SSRI therapy may be a useful strategy for pediatric panic disorder

In the second study, Fairbanks et al²² examined the use of fluoxetine for 6 to 9 weeks in 16 outpatients with mixed anxiety disorders who did not respond to psychotherapy. Patients age ≤12 were given 5 to 40 mg/d and those age ≥13 received 5 to 80 mg/d. Fluoxetine was associated with clinically significant improvement in 3 of the 5 patients who had panic disorder. Although overall fluoxetine was well tolerated, drowsiness, dyssomnia, decreased appetite, nausea, and abdominal pain were the most common side effects. Fluoxetine was not associated with suicidal ideation.

Mixed anxiety disorders

Most trials of pediatric anxiety have evaluated patients with “mixed anxiety disorders” because GAD, social phobia, and separation anxiety disorder are highly comorbid and share diagnostic features (Figure 1).⁹ An RCT of fluvoxamine, up to 300 mg/d, in 128 pediatric patients with ≥1 anxiety disorders found significant differences in CGI-I and endpoint Pediatric Anxiety Rating Scale (PARS) scores.²³ Fluvoxamine was well tolerated but associated with increased motor activity and abdominal discomfort compared with placebo.

Two open-label trials of pediatric patients with mixed anxiety disorders suggested fluoxetine may be beneficial. Fairbanks et al²² documented clinical improvement in 10 of 10 patients with separation anxiety disorder, 8 of 10 with social phobia, 4 of 6 with specific phobia, 3 of 5 with panic disorder, and 1 of 7 with GAD. Birmaher et al²⁴ evaluated 21 pediatric patients with overanxious disorder, social phobia, or separation anxiety who had not responded to psychotherapy and were not depressed; all patients received flexibly-dosed fluoxetine for up to 10 months. Fluoxetine was well tolerated and 81% of patients improved.

Clinical Point

Fluvoxamine or fluoxetine may be helpful for pediatric patients with mixed anxiety disorders

Finally, in a 12-week RCT of 74 patients age 7 to 17 with GAD, separation anxiety disorder, and/or social phobia, fluoxetine, 10 to 20 mg/d, was associated with improved scores on the Screen for Anxiety Related Emotional Disorders, PARS, CGI-I, CGI-S, and Children’s Global Assessment Scale.²⁵ A follow-up open-label trial suggested that maintenance treatment is associated with sustained improvement.²⁶

Figure 1: The pediatric anxiety disorders triad: Comorbidity is common

In the Child-Adolescent Multimodal Treatment Study, GAD was the most common disorder; however, GAD, SAD, and SoP were highly comorbid
GAD: generalized anxiety disorder; SAD: separation anxiety disorder; SoP: social phobia
Source: Reference 9

Anxiety disorders with ADHD

Clinical Point

A multimodal approach that incorporates psychotherapy and pharmacotherapy is more effective than monotherapy

Anxiety disorders often are comorbid with attention-deficit/hyperactivity disorder (ADHD). An RCT of patients age 8 to 17 with ADHD and comorbid anxiety found that atomoxetine was associated with improved PARS scores and ADHD symptoms.²⁷ The target dose was 1.2 mg/kg/d. Atomoxetine was well-tolerated; decreased appetite was the only significant adverse event in the treatment group vs placebo.

Multimodal treatment

Although this article reviews evidence for psychopharmacologic treatments, psychotherapeutic treatment of young patients with anxiety disorders has seen significant advances.²⁸ Most psychotherapy studies have evaluated the efficacy of CBT,^29-31 although there is evidence for psychodynamic therapy and interpersonal therapy.³² The American Academy of Child & Adolescent Psychiatry recommends a multimodal treatment approach because combination treatment appears to be more effective than monotherapy.^8,28,33 Also, clinicians who treat pediatric patients who have an anxiety disorder should evaluate the family’s role on anxiety symptoms and may consider family therapy.

Treatment considerations

Clinical Point

When prescribing SSRIs for pediatric anxiety, monitor patients for suicidality and routinely reassess suicide risk

Evidence supports the efficacy of sertraline, citalopram, paroxetine, fluvoxamine, fluoxetine, and venlafaxine for treating children and adolescents with anxiety disorders (Figure 2).^{8,9,11,15,16,23,25} Some practitioners suggest using differing dosing strategies for pediatric anxiety disorders compared with those used to treat adults (Table).³⁴ When considering SSRIs for children and adolescents, keep in mind the “black-box” warning regarding suicidality in these patients. Carefully monitor patients for treatment-emergent suicidality and routinely reassess for the presence and severity of suicidal ideation and suicide risk.

Figure 2: Number needed to treat for SSRIs and SNRIs in pediatric anxiety disorders