Treating Anxiety Disorders in Children and Adolescents - Presenter: Laura Markley, MD

L A U R A A . M A R K L E Y , M D
Q U A D R U P L E B O A R D - C E R T I F I E D :
P E D I A T R I C S / G E N E R A L P S Y C H I A T R Y / C H I L D & A D O L E S C E N T P S Y C H I A T R Y / A D D I C T I O N M E D I C I N E ;
M E D I C A L D I R E C T O R O F C / L P S Y C H I A T R Y & C O M M U N I T Y P E D I A T R I C L I A I S O N ,
A K R O N C H I L D R E N ’ S H O S P I T A L ;
A S S O C I A T E P R O F E S S O R O F P S Y C H I A T R Y & A S S O C I A T E C L I N I C A L P R O F E S S O R O F P E D I A T R I C S , N E O M E D
Treating Anxiety Disorders in
Children and Adolescents
© Laura A. Markley, MD, FAAP, FAPA, FACLP

Objectives:
 Recognize the signs and symptoms of anxiety disorders
in youth.
 Acknowledge that Psychotherapy is a first-line treatment
for anxiety in children and adolescents and should ideally
always be included in the treatment plan.
 Examine what medications have evidence for use in
treatment of anxiety disorders in children and
adolescents.
 Though there is evidence for several medications, many are not FDA-
approved.
 Discuss when and what medications should be
considered.

What makes anxiety a disorder?
 Worry and anxiety can be developmentally
appropriate:
 Infancy- stranger anxiety
 Toddler- separation anxiety
 Worries about safety as concept of “danger” is introduced in
childhood.
 Social concerns as an adolescent
 The significance of the worry and the amount it
disrupts the child’s ability to function in
developmentally appropriate realms defines whether
it is a disorder.

How Common Are Anxiety Disorders?
 Very common in children- approximately 1: 5-10 children
have an anxiety disorder at any given time.
 The most common mental health disorders in children.
 Often under-diagnosed because the children do not have
the emotional awareness or ability to express what they
are experiencing.
 Young children are especially prone to present with
PHYSICAL SYMPTOMS than older teens and adults.
 If untreated in early childhood, can lead to several issues
in adolescence, including depression, conduct disorder,
ADHD, or other anxiety disorders.

What are the Disorders?
 Historically, studies have tended to group some of the disorders
together because of their similarities in symptomatology and
response to treatment.
 Specific Phobia- treated with exposure-focused therapy- sometimes
medications are used in severe cases, not often.
 Generalized Anxiety Disorder, Separation Anxiety Disorder & Social Phobia
 Panic Disorder
 Obsessive Compulsive Disorder
 PTSD is no longer considered an anxiety disorder, but we will briefly touch
on it because it comes up frequently.

Basic Tenants:
 For most mild to moderate anxiety disorders in
children, Cognitive Behavioral Therapy is first line.
 “Counseling” versus Psychotherapy.
 The only anxiety disorder for which most
medications are FDA-approved in children is
Obsessive Compulsive Disorder, but SSRIs are often
used off-label for the other disorders.
 Duloxetine (an SNRI) recently got FDA approval for GAD in
children over 7 years of age, but current practice dictates that
the SSRIs are still generally used first due to tolerability and
more experience/ evidence with their use.

Treatment – FDA Approval
 FDA approved in pediatric patients
 Obsessive Compulsive Disorder
 Clomipramine (Anafranil ®): 10-17
 Fluoxetine (Prozac ®): 7-17
 Fluvoxamine (Luvox ®): 8-17
 Sertraline (Zoloft ®): 6-17
 Generalized Anxiety Disorder:
 Duloxetine (Cymbalta ®) ages 7 (+)

Treatment – FDA Approval:
 NOT FDA approved:
 Paroxetine (Paxil)
○ 2003: FDA recommends paroxetine NOT be used in children with
MDD (risk of suicide, lack of efficacy)
 Citalopram (Celexa)
 Lexapro is approved for Major Depression in Children 12 and up, but
not anxiety disorders.
 Venlafaxine (Effexor)
 2003 – Wyeth warns providers against use in children and adolescents
 Bupropion (Wellbutrin)
 Mirtazapine (Remeron)
 Buspirone (BuSpar)

Generalized Anxiety Disorder, Separation
Anxiety Disorder & Social Phobia
 Several placebo-controlled trials support the use of
antidepressant medications in youth with anxiety
disorders, with most supporting SSRIs as first-line.
 Studies have demonstrated efficacy of fluoxetine
(Prozac®); sertraline (Zoloft®); fluvoxamine (Luvox®);
and paroxetine (Paxil®).
 Sertraline has the greatest evidence of efficacy.
 Paxil has fallen out of favor as a first line treatment due to adverse
effects, short half-life, and a concern that paroxetine and venlafaxine
(an SNRI) had more treatment –emergent suicidal thinking when
treated for anxiety. US warning issued against Paxil in children in
2003 and European warning in 2004.

 Child-Adolescent Anxiety Multimodal Study (CAMS):
 Treatment of SAD, GAD, or Social Phobia with one of four treatment
arms- CBT; sertraline; CBT (+) sertraline; and a placebo arm.
 Results were “superior clinical improvement” over 12 week period:
 CBT: 59.7%
 Sertraline: 54.9%
 Combination: 80.7%
 Placebo: 23.7%
 Authors concluded that all three treatment arms could be reasonable
to consider for non-OCD anxiety illnesses in children.
 Just a reminder that sertraline is still considered “off-label.”
Not statistically significant

 SNRIs:
 Venlafaxine XR:
 Placebo controlled studies have not been consistently conclusive and response is less robust
compared to placebo (69% vs 48%).
 Current guidelines recommend consideration only after failure with several SSRIs with close
monitoring for adverse effects.
 Duloxetine:
 Is FDA-approved for GAD in ages 7 and up, but still not considered first-line.
 Generalized Anxiety Disorder – Efficacy was demonstrated in one 10-week, placebo-controlled
trial in 272 patients age 7 to 17 years. Cymbalta® demonstrated superiority over placebo as
measured by greater improvement in the Pediatric Anxiety Rating Scale for GAD severity
score. The safety and effectiveness in pediatric patients less than 7 years of age have not been
established.
 Major Depressive Disorder – Efficacy was not demonstrated in two 10-week, placebo-
controlled trials with 800 pediatric patients with MDD, age 7-17.
 The most common (≥5% and twice placebo) adverse reactions observed in pediatric clinical
trials include: nausea, diarrhea, decreased weight, and dizziness

 Tricyclics:
 Studies have been inconclusive as to whether these medications are helpful in these disorders.
 These medications risk cardiac arrhythmias and can be lethal in overdose. Should not be considered for
these particular anxiety disorders. Should be used with caution in other scenarios.
 Benzodiazepines:
 Despite MULTIPLE trials have NEVER been proven to be efficacious as single agents for treatment
of anxiety disorders in youth.
 Can be used to target anxiety symptoms during titration of antidepressants:
 Use only in select cases-screen for risk of abuse and consider the risk of the environment as well.
 Can cause cognitive dulling, decreased academic performance, sleep cycle disruptions, disinhibition and
increased risk of accidental injury.
 Buspar:
 No controlled trials but a couple small open-label ones were promising.
 Children do better with small dose (5 -7.5 mg po BID) where adolescents seem to need more (5- 30
mg po BID).
 Side effects in the studies were lightheadednesss (68%); headache (48%) and dyspepsia (20%).

 Strongest predictors of remission with treatment:
 Lack of other internalizing disorders (like depression)
 Lower baseline anxiety levels (so, not as severe when treatment
initiated)
 Younger age
 Lack of Social Phobia
 Non-minority status

Panic Disorder:
 Unfortunately, no placebo-controlled trials.
 One open study showed significant improvements in up
to 75% of patients on various SSRIs- fluoxetine,
sertraline, and paroxetine (but we don’t use paroxetine);
the SSRIs were used alone or in combination with short-
acting benzos (alone preferred).
 Another study (also open) of mixed anxiety disorders
showed fluoxetine effective in several anxiety symptoms
in children, including panic. Mean dose for children was
24 mg and the mean dose for adolescents was 40 mg.

Obsessive Compulsive Disorder (OCD):
 Can be very difficult to treat.
 Strong familial association (12% first degree relative) so
family may also have poor insight into the degree of
functional compromise.
 For mild symptoms, CBT is recommended.
 For moderate to severe symptoms, combined treatment
is recommended. This is where you have the most “on-
label” choices, remember? (sertraline, fluoxetine,
fluvoxamine, and clomipramine).
 Also consider medication early-on if mild symptoms but
comorbid disorders, like depression or other anxiety
issues are present.

 Metanalysis showed significant symptomatic
improvement with SSRI treatment, though no one SSRI
distinguished itself.
 POTS (Pediatric OCD Treatment Study):
 Treatment of OCD with one of four treatment arms- CBT; sertraline;
CBT (+) sertraline; and a placebo arm.
 Results were “clinical remission” after a 12 week period:
 CBT: 39.3%
 Sertraline: 21.4%
 Combination: 53.6 %
 Placebo: 3.6%
 Authors concluded that “children with OCD should begin treatment
with the combination of CBT and an SSRI, or with CBT alone.”

 Clomipramine:
 Has been FDA approved for OCD since 1989.
 Works better than less serotonergic TCAs, like desipramine.
 May be more efficacious than the SSRI’s in treating OCD, but
still not considered first line because of potential side effects
and lethality in overdose.
 Other agents for the treatment/ augmentation of treatment-
resistant OCD are beyond the scope of this talk.

Post Traumatic Stress Disorder
 Has been changed from an anxiety disorder to its own
branch of pathology in the DSM-V.
 Greater than 1 in 4 children will experience some type of
trauma prior to adulthood.
 SSRIs have shown limited to negligible benefit compared
to placebo in childhood PTSD. They are considered “an
option” but not first line.
 Trauma-focused CBT is the first line treatment for PTSD
in youth.
 However, if patient has depression or other co-morbid
anxiety, SSRI’s may be more helpful.

How do I find a good therapist?
 Patient can look for covered therapists on their
insurance company website.
 Consider local mental health agency if patient/
family need more intensive and potentially home-
based interventions.
 https://www.psychologytoday.com/us/therapists

SSRI Treatment Pearls:
 “Start low, go slow”
 Starting dose for 3-7 days, then increase to full
dose as tolerated
 Typical starting doses (adolescent population):
 Sertraline
○ 25 mg daily for 3-7 days, then 50 mg daily
○ Ballpark between 75 mg to 125 mg daily for most anxiety
disorders.
○ Fluoxetine
 10 mg daily for 3-7 days, then 20 mg daily, may need to increase
to higher doses in anxiety. (20 mg average for children, 40 for
adolescents)

 Typical starting doses (adolescent population):
 Citalopram
○ 10 mg daily for 3-7 days, then 20 mg daily
○ - most anxiety studies used higher doses, but higher doses aren’t great
because of some risk of QTc prolongation after 40 mg daily.
 Escitalopram
 In young children or small adolescents, start at 5 mg per day for 3-7 days,
then increase to 10 mg with increase to 20 mg if needed.
 20 mg daily will usually be needed for anxiety in adolescents.
 Liquid Formulations
 Allow lower doses / more flexible dosing
 Available for: Fluoxetine, Escitalopram, Citalopram, Sertraline

 Select advantages/disadvantages
 Sertraline
○ Advantages: Low cost, Most evidence for efficacy in anxiety disorders
○ Disadvantages: Shorter half life, GI side effects more common
 Fluoxetine
○ Advantages: Longer half life, low cost
○ Disadvantages: More activating, more drug interactions (2D6)
 Escitalopram
○ Advantages: Titration often not necessary, minimal side effects, helpful in medically
complex patients (few interactions)
○ Disadvantages: higher cost- generic, but not $4
 Citalopram
○ Advantages: Minimal side effects, low cost
○ Disadvantages: Shorter half life (still seems to work well), potential QTc prolongation at
doses of ≥ 40 mg per day

 Select advantages/disadvantages
○ Duloxetine:
○ Advantages: FDA approved for generalized anxiety in ages 7 and up based on one 10 week
study.
○ Disadvantages: More side effects, may elevate B/P, showed no improvement in depressive
symptoms in children, withdrawal effects
 Venlafaxine
○ Advantages: Minimal to none.
○ Disadvantages: More side effects, may elevate B/P
 Bupropion
○ Advantages: None- No studies, often worsens sleep and anxiety.
○ Disadvantages: Dosing less flexible, worsens sleep, not helpful for anxiety,
contraindicated in eating disorders (lowers seizure threshold)

• Half lives may be shorter in children
• Some medications may need to be dosed BID in
very young children, but not usually.
 Citalopram
 Sertraline
 Withdrawal / Discontinuation Symptoms
 Irritability
 Flu-like symptoms
 Fatigue
 Electric-shock sensations

 Response time:
 Some report improvement in several days
 Up to 6 weeks for first response
 Up to 12 weeks for sustained response
 Anxiety generally takes larger doses for longer periods of
time to see a response than with depression.
 If depression and anxiety co-exist, consider medication early
on in the course.

 Assess response at 4-week intervals
 Increase dose at week 4 if partial response
 Consider changing medications if:
 no response after 4 weeks on a therapeutic dose:
 For example: 12.5 mg of sertraline in a teenager is not a therapeutic dose.
The time clock for “not effective” shouldn’t start until you have tried at 50 mg
for up to 4 weeks.
 minimal response after 8 weeks
 remission can take longer than with depression, but in most studies most
demonstrated good response at 12 weeks at a therapeutic dose of medication.

 Treatment duration for anxiety:
 Continue medication for 12 to 18 months after
remission
 CBT often needed to help maintain response
 Discontinuation symptoms:
 More common with medications with shorter half lives
 Very uncommon with fluoxetine
 Avoid by slowly tapering medication
 Can occur after just 6-8 weeks of treatment

SSRIs: The Black Box
 The Black Box Warning:
 WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
 Antidepressants increased the risk compared to placebo of suicidal thinking and behavior
 (suicidality) in children, adolescents, and young adults in short-term studies of Major
 Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use
 of fluoxetine tablets or any other antidepressant in a child, adolescent, or young adult must
 balance this risk with the clinical need. Short-term studies did not show an increase in the
 risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there
 was a reduction in risk with antidepressants compared to placebo in adults aged 65 and
 older. Depression and certain other psychiatric disorders are themselves associated with
 increases in the risk of suicide. Patients of all ages who are started on antidepressant
 therapy should be monitored appropriately and observed closely for clinical worsening,
 suicidality, or unusual changes in behavior. Families and caregivers should be advised of
 the need for close observation and communication with the prescriber.

 The Black Box Warning: based on a review of 24 short-
term randomized controlled trials with SSRIs in
children for any indication.
 This review found there was a two-fold increased risk
of suicidal thoughts or behaviors while taking a SSRI
versus taking a Placebo.
 4% risk with antidepressant treatment
 2% risk with placebo
 No completed suicides

 In the literature:
 No correlation between antidepressants and completed suicides
 Rating scales indicate decline in suicidality with antidepressant
treatment
 Increase was found with “spontaneously reported suicidality”
 Number needed to harm in depression: 112
 Number needed to harm in anxiety: 143
 Antidepressant use has been linked to decrease in suicide rate.
 2 meta-analyses of patients treated with SSRIs for anxiety failed to
identify a increased risk of treatment-emergent suicidality.
 Paroxetine and Venlafaxine have had more incidences of
treatment-emergent suicidality in anxious patients compared to
placebo, another reason these medications are not favored.

SOURCES
Primary Sources:
Peters TE, Connolly S. Psychopharmacologic Treatment for Pediatric Anxiety Disorders. Child Adolesc Psychiatr Clin N Am. 2012. Oct; 21 (4):789-806. doi 10.1016/j.chc.2012.07.007.
Strawn JR, Dobson ET, Giles LL. Pediatric Primary Care Psychopharmacology: Focus on Medications for ADHD, Depression, and Anxiety. Curr Probl Pediatr Adolesc Health Care 2017
Jan; 47 (1) 3-14. doi 10.1016/j.cppeds.2016.11.008. Epub 2016 Dec 30.
Strawn JR, Sakolsky DJ, Rynn MA. Psychopharmacologic Treatment of Children and Adolescents with Anxiety Disorders. Child Adolesc Psychiatr Clin N Am. 2012. Jul; 21 (3):527-539.
doi 10.1016/j.chc.2012.05.003.Epub 2012 May 24.
Secondary Sources:
American Academy of Child and Adolescent Psychiatry. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. Journal of the American
Academy of Child and Adolescent Psychiatry. 2007;46(11):1503-1526.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental disorders, 4th edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
[An update on depression in children and adolescents]. Journal of Clinical Psychiatry. 2008;66(11):1818-1828.
Baer, Daniel. “Psychopharmacology Update.” 4th Ann. Development, Behavior and Emotions: Enhancing Care in the Medical Home. 4/8/10
Emslie G, Kratochvil C, Vitiello B, Silva S, Mayes T, McNulty S, Weller E, Waslick B, Casat C, Walkup J, Pathak S, Rohde P, Posner K, March J. Treatment of adolescents with depression
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Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, Rintelmann J. A double-blind, randomized, placebo-controlled study of fluoxetine in depressed children and
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