Depression Pearls for Pediatric Providers - 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
Depression Pearls for Pediatric Providers
© Laura A. Markley, MD, FAAP, FAPA, FACLP

Depression Pearls:
 Differences in Pediatric patients:
 Mood can be irritable instead of depressed
 Change from baseline
 Less likely to verbalize symptoms
 Behavioral changes more common
 Temper tantrums
 Social withdrawal
 Somatic symptoms more common
 Headaches, stomachaches are the most frequent symptoms

Depression Pearls:
 Mild Depression:
 No suicidal ideation / behaviors
 No psychotic symptoms
 Anhedonia not prominent
 Hopelessness not prominent
 Supportive treatment may be sufficient
 Supportive therapy
 Psychoeducation
 Managing environmental stressors
 Monitor for improvement over 4-6 weeks
 Consider more aggressive treatment if ineffective

Depression Pearls:
 Moderate to Severe Depression
 The most effective treatment includes medication
or combination of medication and therapy

PHQ-9 SCREENING

PHQ-9 SCORING
To use the PHQ-9 as a diagnostic aid for Major Depressive Disorder:
 Questions 1 and/or 2 need to be endorsed as a “2” or “3”
 Need five or more positive symptoms (positive is defined by a “2” or “3” in questions 1-8 and by a “1”, “2”, or
“3” in question 9).
 The functional impairment question (How difficult….) needs to be rated at least as “somewhat difficult.”
To use the PHQ-9 to screen for all types of depression or other mental illness:
 All positive answers (positive is defined by a “2” or “3” in questions 1-8 and by a “1”, “2”, or “3” in question 9)
should be followed up by interview.
 A total PHQ-9 score > 10 (see below for instructions on how to obtain a total score) has a good sensitivity and
specificity for Major Depressive Disorder.
To use the PHQ-9 to screen for suicide risk:
 All positive answers to question 9 as well as the two additional suicide items MUST be followed up by a clinical
interview. The PHQ-9 is not considered a reliable independent suicide screening tool.
To use the PHQ-9 to obtain a total score and assess depressive severity:
 Add up the numbers endorsed for questions 1-9 and obtain a total score.
 Total Score Depression Severity:
0-4: No or Minimal depression
5-9: Mild depression
10-14: Moderate depression
15-19: Moderately severe depression
20-27: Severe depression

SSRIs: They work!!
 TADS (Treatment of Adolescents with
Depression Study):
 For Teens with Moderate to Severe Depression, the most
effective treatment was combination of medication and CBT
OR Medication alone:
 CBT + Fluoxetine (Prozac): 71% response (62 to 80%= 95%CI)
 Fluoxetine alone: 60.6% response (51 to 70%= 95%CI)
 CBT alone: 43.2% response (34 to 52 %= 95%CI)
 Placebo: 34.8% response (26 to 44 %= 95%CI)

Treatment – FDA Approval
 FDA approved in pediatric patients
 Major Depressive Disorder
 Escitalopram (Lexapro): Ages 12-17
 Fluoxetine (Prozac): 8-17
 Obsessive Compulsive Disorder
 Clomipramine (Anafranil): 10-17
 Fluoxetine (Prozac): 7-17
 Fluvoxamine (Luvox): 8-17
 Sertraline (Zoloft): 6-17

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)
○ Has NEVER been shown to have a positive effect in any study done on
Pediatric patients.
○ DO NOT PRESCRIBE this medication!!!!
 Citalopram (Celexa)
 Venlafaxine (Effexor)
 2003 – Wyeth warns providers against use in children and adolescents
 Bupropion (Wellbutrin)
 Duloxetine (Cymbalta)
 Mirtazapine (Remeron)
 Buspirone (BuSpar)

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):
 Fluoxetine
 10 mg daily for 3-7 days, then 20 mg daily
 Escitalopram
 In young children or small adolescents, start at 5 mg per day for
3-7 days, then increase to 10 mg.
 10 mg daily

 Typical starting doses (adolescent population):
 Citalopram
○ 10 mg daily for 3-7 days, then 20 mg daily
 Sertraline
○ 25 mg daily for 3-7 days, then 50 mg daily
 Liquid Formulations
 Allow lower doses / more flexible dosing
 Available for: Fluoxetine, Escitalopram, Citalopram,
Sertraline

 Select advantages/disadvantages
 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
 Sertraline
○ Advantages: Low cost, helpful in anxiety disorders
○ Disadvantages: Shorter half life, GI side effects more
common
 Venlafaxine
○ Advantages: Minimal to none.
○ Disadvantages: More side effects, may elevate B/P
 Bupropion
○ Advantages: questionably beneficial in ADHD, decrease nicotine craving
○ Disadvantages: Dosing less flexible, 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
 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
 If anxiety also present, takes larger doses for longer periods
of time to see a response.

 Assess response at 4 week intervals
 Increase dose at week 4 if partial response
 Consider changing medications if:
 no response after 4 weeks
 minimal response after 8 weeks
 remission has not occurred after 12 weeks
 Of those who do not respond to an initial antidepressant,
50% respond to a second

 Treatment duration after 1st depressive episode:
 Continue medication for 6-12 months after remission
 CBT may 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: Adverse Effects
 Other Adverse Effects are Much More Common, but
are overshadowed by the Black Box.
 Most common:
 changes in alertness (insomnia or sedation);
 appetite (increase or decrease);
 gastrointestinal symptoms (nausea, constipation, dry mouth);
 restlessness;
 diaphoresis;
 headaches;
 sexual dysfunction

SSRIs: Adverse Effects :
 Mania
 Incidence likely < 1%
 Some studies have indicated SSRI’s may induce mania, but
incidence too small to be statistically significant
 Generally occurs after 2-4 weeks of treatment
 Grandiosity / inflated self esteem
 Decreased need for sleep
 Racing thoughts and speech
 Development of activation or manic symptoms does
not necessarily mean the child has bipolar disorder

SSRIs: Other Adverse Effects
 “Behavioral activation” commonly occurs in children at a
rate of ~5%,and is reversible with discontinuation
 Rare increased risk of bleeding- possibly relevant if surgery
is planned or on other potentially anti-coagulant
medication.
 Rare risk of serotonin syndrome- usually in overdose or
combination with other serotonergic meds.
 Certain SSRIs have potential to prolong the QTc interval-
caution in history of familial prolonged QT or with other
QTc-prolonging agents.

SSRIs: Adverse Effects
 Select side effects:
 Headache
 Vomiting*
 Abdominal Pain*
 Insomnia*
 Somnolence*
 Nausea
 Tremor
 Agitation
 Restlessness / increased
anxiety
 Irritability
 Vivid dreams
 Bruxism
 Increased predisposition
to bleeding
*TADS study, > 2incidence, > 2x rate of placebo

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 large studies:
 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: 112
 Antidepressant use has been linked to decrease in suicide
rate

SSRIs DO NOT increase suicide.
 Utah Youth Suicide Study: Demonstrated that
almost all youth in the study, which looked only at
completed suicides and did retrospective profiles,
were not in treatment or not adherent to treatment/
not taking their medications.
 Population studies in multiple countries have
demonstrated an overall DROP in suicide
rates with introduction of SSRIs.

SSRIs DO NOT increase suicide.
 Treatment of Adolescent Depression Study:
 At baseline
29% reported suicidal ideation
21% exhibited suicidal behavior
 Measures of suicidal ideation improved in all
groups
 Greatest improvement in combination treatment
 No Completed Suicides

Untreated Depression CAN increase suicide.
 After the Black Box warning:
 Antidepressant prescriptions to pediatric patients declined
 10% decline overall
 40% decline in primary care
 Diagnosis of depression in pediatric patients declined
 44% decline in primary care
 Those diagnosed with depression were 3 times less likely to receive
medication
 No concomitant increase in other treatments (i.e., therapy)
 Suicide rate in pediatric patients increased
 18% increase from 2004 to 2005
 1st increase in 10 years

Monitoring SSRIs: How Often?
 Monitor closely when starting, stopping, or changing
doses of medication
 FDA used to recommend: Weekly x 1 month, then
biweekly until symptoms resolve, then monthly
 Now recommendation is “monitored appropriately
and observed closely” during the initial few months of
treatment
 Usually:
 At least phone contact within 1-2 weeks of starting the
medication, then re-assess at 4 weeks, then usually in
4-6 week intervals.

Monitoring SSRIs:
 What to Monitor and Document:
 Screen for new suicidal thoughts- every visit.
 Height & weight- plot growth curve at every visit
 Ask about new easy bruising or bleeding
 Inquire about sleep issues, new irritability and agitation,
restlessness- every visit, but especially at week two and
after 4-6 weeks.
 Consider Using a Rating Scale to Monitor progress (for
example, patient and parent can complete the PHQ-9 in
the waiting room and it doesn’t take extra time in the
appointment).

Documenting Consent or Refusal:
 Especially in the age of EMR’s, one can have a smart-
phrase saved to help document.
 An example for SSRI consent is:
 “ Discussed the risks, benefits, and alternatives to the use
of antidepressant medication, as well as the expected
outcomes with and without medications. Discussed the
possible risk of suicidal thinking and behavior in
children and adolescents treated with antidepressants.
Also discussed risk of behavioral activation, as well as
physical complaints such as headache or upset stomach.
Guardians expressed understanding, and provided
consent to begin treatment with medication.”

Documenting Consent or Refusal:
 If a parent declines to start a medication that you feel
the patient would benefit from, document that too!
 “This provider recommended that the patient be placed on an
SSRI, as the most effective and robust treatment for moderate
to severe depression in teenagers is that of combined
treatment with psychotherapy and antidepressant
medication. Parents and patient have opted to decline
initiation of an SSRI at this time, but are strongly encouraged
to re-visit this option if the patient's symptoms do not
improve or worsen in the near future.”

Depression 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
 CAP PC New York. Scoring the PHQ-9 Modified for Teens www.cappcny.org/home/documents/phq 9 teens scoring.pdf Accessed 6/28/16.
 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 study (TADS): Safety results. Journal of the American Academy of Child and Adolescent Psychiatry. 2006;45(12):1440-1455.
 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 adolescents. Archives of General Psychiatry. 1997;54:1031-1037.
 Emslie GJ, Ryan ND, Wagner KD. Journal of Clinical Psychiatry. 2005;66(Suppl 7):14-20.
 Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant medication use and rate of suicide. Archives of General Psychiatry.
2005;62:165-172.
 Hammad TA, Laughren, T, Racoosin, J. Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry. 2006;63:332-339.
 Kratochvil C, Emslie G, Silva S, McNulty S, Walkup J, Curry J, Reinecke M, Vitiello B, Rohde P, Feeny N, Casat C, Pathak S, Weller E, May D, Mayes T, Robins
M, March J. Acute time to response in the Treatment for Adolescents With Depression Study (TADS). Journal of the American Academy of Child and Adolescent
Psychiatry. 2006;45:1412-1418.
 Libby AM, Brent DA, Morrato EH, Orton HD, Allen R, Valuck RJ. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with
SSRIs. American Journal of Psychiatry. 2007;164(6):884-91.
 Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Archives of General Psychiatry. 2009;66(6):633-9.
 Olfson M, Shaffer D, Marcus SC, Greenberg T. Relationship between antidepressant medication treatment and suicide in adolescents. Archives of General
Psychiatry. 2003;60:978-982.
 Ryan ND. Treatment of depression in children and adolescents. Lancet. 2005;366:933-940.
 TADS. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS)
randomized controlled trial. JAMA 2004;292:807-820.
 Tsapakis, EM, Soldani, F, Tondo, L, Baldessarini, RJ. Efficacy of antidepressants in juvenile depression: meta-analysis. The British Journal of Psychiatry.
2008;193:10-17.

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