The typical first line treatment for mild GAD is psychotherapy, specifically Cognitive Behavioral Therapy (CBT). For moderate and severe GAD, combination therapy and medication has demonstrated superior efficacy to either treatment alone. Interestingly, the only medication FDA approved for pediatric GAD is Duloxetine (Cymbalta), approved for ages 7-17. However, in practice, SSRI medication remains the typical first line pharmacologic intervention. There is no evidence that any SSRI is more effective than another. Fluoxetine (Prozac), Sertraline (Zoloft), and Escitalopram (Lexapro) are the most commonly prescribed, though Fluvoxamine (Luvox), Paroxetine (Paxil), and Venlafaxine (Effexor) have all shown efficacy in placebo-controlled trials. A typical algorithm (for medication intervention) is first SSRI, if not effective second SSRI, and if again not effective SNRI.
A typical PAL consult is what to do when the second SSRI is not effective or not tolerated. In a typical case, Duloxetine would be the recommendation, as this has shown efficacy in placebo-controlled trials, and has the FDA approval. Things become trickier if Duloxetine is not tolerated or not helpful. In this case, I would want to make sure Duloxetine is appropriately dosed. If there is no benefit at 60mg for 4-6 weeks, I would consider this a failed trial. However, if there is a partial response at 60mg, increasing to 90-120mg is reasonable, though doses above 60mg have not been found via placebo-controlled trial to provide additional benefit .
Benzodiazepines, while clearly efficacious and approved for adult GAD, have not shown clear benefit for the pediatric population . For pre-pubertal children, these are known to have disinhibiting properties. I reserve benzodiazepine use for severe adolescent cases with clear functional impairment, active and trustworthy parents to help with administration, and no personal history of substance abuse. These should obviously be outlined as a short-term treatment to be used while the SSRI/SNRI are building up. I typically start with Clonazepam 0.25mg given bid-tid, either PRN or scheduled.
An alternative “PRN” medication for GAD is Hydroxyzine (Vistaril, Atarax). I have found 25mg to be sedating for many children, so usually start with a 10mg dose given tid PRN. This can be titrated up to 50mg per dose.
The non-SSRI Buspirone (Buspar) was studied in an unpublished placebo-controlled trial (N=559). No statistically significant difference with Buspar and placebo was observed. There are case reports of successful treatment of GAD with Buspar, and it has been shown to be well-tolerated. In a primary care setting, I would reserve this for adolescents, starting dose of 7.5mg bid, increased by 5-10mg per week to max of 30mg bid .
For the child with comorbid ADHD, and/or “activation” with SSRI/SNRI treatments, Guanfacine extended-release (Intuniv), an alpha 2A –adrenergic receptor agonist, may be a reasonable alternative. Agents that decrease norepinephrine release may decrease the fear response, producing anxiolytic effects. A recent study by JR Strawn, et al. , aimed to demonstrate safety and tolerability, and potential efficacy of this medication. It was shown to be well-tolerated, with most common side effects of headache, fatigue/somnolence, abdominal pain, and dizziness. No significant difference was observed compared to placebo on the PARS (pediatric anxiety rating scale) or SCARED (screen for child anxiety related emotional disorders) scales. There was improvement in the Clinical Global Impression-Improvement (CGI-I) score with Intuniv versus placebo. Overall, this study was under-powered to show direct evidence of efficacy. Doses used in this trial were 1-6mg daily.
- Green’s Child and Adolescent Clinical Psychopharmocology, Fifth Edition. Pages 302-314.
- Hussain FS, et al. Pharmacologic Treatment of Pediatric Anxiety Disorders. Curr Treat Options Psychiatry. 2016 Jun; 3(2): 151–160.
- Strawn JR, et al. Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis. Depress Anxiety. 2015 Mar;32(3):149-57.
- Strawn JR, et al. Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial. Journal of Child and Adolexcent Psychopharmacology. 2017 Volume 27, Number 1: 29-37.
- Strawn JR, et al. A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2015 Apr;54(4):283-93