Treatment of Depression in Children

1
Treatment of Depression in Children Adolescents

• Saundra Stock, M.D.
• USF Department of Psychiatry Neurosciences
• Program Director, Child and Adolescent Psychiatry
  Residency

2
Learning Objectives

• Be able to recognize various symptoms of a major
  depressive episode
• Know the typical course of depression
• Know common interventions for depression based on
  symptom severity
• Learn 5 supportive strategies for primary care
  providers to implement in the office
• Know the top 4 medications choices used to treat
  depression in youth
• Understand the risk of suicide with medication
  treatment for depression

3
Depression

• Affect 2.6 million youth ages 6-17 annually
• 2.5 children (MF 11)
• 8.3 adolescents (MF 12)
• 40-80 experience suicidal thoughts
• 35 of depressed youth will attempt suicide
• Affects every facet of life - peers, family,
  school and general health

4
How depressive symptoms manifest?

• Mood
• Depressed or irritable mood
• Mood labiality
• Behavior
• Kids may not verbalize sadness but show low
  frustration tolerance, social withdrawal or
  somatic complaints
• ? interests (stop sports activities etc.) c/o
  boredom
• Vegetative symptoms
• Fatigue or ? energy
• Sleep disturbance (often hypersomnia)
• Wt change, appetite change
• PMA or PMR
• ? concentration or indecisiveness
• Cognition
• Feelings of worthless/hopeless or inappropriate
  guilt
• Thoughts of death or suicide

5
Criteria for Major Depressive Episodedepressed
mood or anhedonia 4 others

• S -
• I -
• G -
• E -
• C -
• A -
• P -
• S -

6
Criteria for Major Depressive Episodedepressed
mood or anhedonia 4 others

• S - sleep, insomnia or hypersomnia
• I - interests
• G - guilt, feeling worthless or hopeless
• E - energy
• C - concentration
• A - appetite
• P - psychomotor retardation or agitation
• S - suicidal thoughts or recurrent thoughts of
  death

7
Symptom variation based on age

• At all ages depressed mood, I dont care,
  bored, ?concentration, insomnia ? SI
• Children gt somatic complaints, separation
  anxiety, PMA, phobias, sad affect, auditory
  hallucinations
• Teens gt anhedonia, hopelessness, drug abuse/self
  destructive behavior or atypical depression
  pattern
• ?sleep,?appetite, leaden paralysis (PMR)
  interpersonal rejection sensitivity

8
When do we see depression?

• Depression more common with ? age but described
  even in infants
• Bowlby - depression in institutionalized infants
  had sleep disturbance, ?feeding, listless,
  withdrawn
• protest, anxiety, despair, detachment
• Is depression in children adolescents the same
  illness as in adults?
• Recent studies show it is continuous with the
  adult disease with high relapse rates for those
  1st episode in childhood

9
Gathering History

• Best to interview both parent and youth
• Parents better at reporting behavioral
  disturbances time course of symptoms
• Youth better at reporting on mood/anxiety/sleep
• Youth often have depressed mood or SI that parent
  is unaware of
• Youth depression inventory-self admin scales
• Childrens Depression Inventory (CDI)
• CES-DC (public domain)
• BDI-II
• PHQ-9 (GLAD-PC toolkit, public domain 73
  sensitivity 98 specificity)

10
Gathering History youth self report

• PHQ-2 questions scored on 3 point scale
• 0 not at all and 3 nearly every day
• Comparable to PHQ-9
• In the past 2 weeks have you experienced
• Have you been feeling sad or depressed for the
  past 2 weeks?
• Do you have a lack of pleasure in usual
  activities in past 2 weeks?
• Score gt3 sensitivity 74 and specificity 75

11
Gathering history

• R/O neglect, abuse physical or sexual
• Recent stressors
• Anxiety symptoms
• Unusual thoughts or psychotic symptoms prodrome
  to schizophrenia
• Symptoms of mania now or past
• ? need for sleep, hypersexuality or grandiosity
• FHx of suicides or bipolar disorder

12
Genetics

• Depression runs in families
• Monozygotic twin 76 concordance, raised
  separately 67 concordance
• Children with one depressed parent are 3x more
  likely to have MDD than children of non-depressed
  parents
• Need to ask about family history of bipolar
  disorder

13
Effects of depressed parents

• Depressed children tend to have poor
  relationships (family and friends) often have
  depressed parents.
• Depression in parents associated with child
  depression (mothers ?fathers).
• Depressed parents may over-report concerns
  (focus on negative aspects) or under-report (too
  depressed to attend to or observe child
  accurately)
• Study by Hammen et al - children exposed to
  substantial stress, those with mothers with
  depression did worse than those with just the
  stress
• STARD study children sxs improved with Moms
  esp if Mom remitted within 3 months of tx

14
Differential

• Infectious
• Mononucleosis
• Influenza
• TB
• Hepatitis
• Syphilis
• HIV
• Subacute endocarditis

• Neurologic
• Epilepsy
• CVA
• Multiple sclerosis
• Postconcussive states
• Subarachnoid hemorrhage
• Huntingtons disease
• Wilsons disease

15
Differential (contd.)

• Endocrine
• Diabetes
• Cushings disease
• Addisons disease
• ?or?thyroid
• ?parthyroid
• ? pituitary function

• Others
• Lupus
• Porphyria
• ?sodium
• ?potassium
• Anemia
• Etoh or drug abuse
• Meds-steroids,OCP,cimetidine, BDZ, antiHTN,
  aminophylline

16
Co-morbid psychiatric disease and differential

• 40-90 co-morbid conditions dysthymia, anxiety
  disorder, disruptive behavioral disorders, ADHD
  or substance abuse
• Prediction of bipolar disorder - early onset, ?
  PMR, psychotic features, FHx ? bipolar, FHx
  psychotic depression, drug induced hypomania

17
Work-up

• History
• Physical exam
• CBC, electrolytes, LFTs, TSH, UA and B12,
  vitamin D
• Consider UDS
• Consider other labs/tests as indicated folate,
  RPR, ESR, HIV, creatinine clearance, EEG

18
Course of Major Depression

• Median duration of an episode 8 months in
  clinically referred youth, community samples 1-2
  months
• 70 of pts have a recurrent MDE within 5 years.
• 20-40 will develop bipolar disorder

19
Course of Major Depression

• Prediction of relapse
• early age onset
• ? previous episodes
• severity
• psychosis
• lack of compliance

• Poor prognosis
• ? symptom severity
• Chronicity or ? relapses
• Residual symptoms
• Negative cognitive style or hopelessness
• Psychiatric comorbidity
• Low SES
• Family problems
• Ongoing negative life events

20
Sequelae

• Depression untreated affects social, emotional,
  cognitive and interpersonal skills
• Any episode 7-9 months is a long time in
  adolescents life
• High risk for nicotine substance dependence,
  early teen pregnancy, physical illness
• As adults, higher suicide rates, more medical
  psychiatric hospitalization, more impairment in
  work, family and social life

21
Treatment

• Psychoeducation
• Parents
• School
• Individual psychotherapy
• Supportive
• Cognitive Behavioral Therapy
• Interpersonal Psychotherapy
• Family therapy
• Medication

22
Treatment Goals

• Response significant reduction in symptoms or
  no symptoms for 2 weeks
• Remission period of gt 2 weeks and lt 2 months
  with few symptoms
• Recovery absence of sxs for gt 2 months
• Recovery is the goal

23
Treatment recommendations initial steps
Positive screening for MDE and subsequent
diagnosis
Psychoeducation and treatment planning
Mild depressive to moderate sxs Active support
and monitoring for 6-8 weeks
Moderate to severe depressive sxs Begin
evidence based therapy or medication or both for
6-8 weeks
Severe depressive sxs Start medication and
referral
AACAP practice parameters 2007 and GLAD-PC 2007
24
Psychoeducation

• All patients should receive
• Information about symptoms and typical course
  with discussion (depression is a illness not a
  sign of weakness no ones fault etc.)
• Discussion of treatment options
• Placing pt in sick role temporarily may be
  helpful and temporary school accommodations
• No controlled trials with just psychoeducation,
  however, many pts improve with only education and
  supportive care

25
Supportive Treatment

• All patients should receive and may be all that
  is required for mild depressive sxs
• Meeting frequently to monitor progress
• Active listening and reflection
• Restoration of hope
• Problem solving
• Improving coping skills
• Strategies for adherence
• If not improving in 4 weeks, more to a more
  specific treatment

26
Treatment Options

• If has moderate to severe depression, start with
  more specific treatment OR if mild to moderate
  depression not improving after 4 weeks of
  supportive care (watchful waiting)
• Individual psychotherapy
• Cognitive Behavioral Therapy
• Interpersonal Psychotherapy
• Family therapy
• Medication
• Severe depression start meds and other
  referrals

27
Medication Treatment Options

• Selective Serotonin Reuptake Inhibitors
• Selective NE Reuptake Inhibitors
• Other antidepressants
• Tricyclic Antidepressants
• Typical duration of medication treatment 6 to
  12 months after response present. Relapse high if
  stop within 4 months of symptom improvement.

28
Medication-SSRIs

• Fluoxetine (Prozac) - age 8
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Citalopram (Celexa)
• Escitalopram (Lexapro) - age 12
• Fluvoxamine (Luvox)
• FDA approved for the treatment of MDD under age
  18

29
Medication - SSRIs

• Early studies - struggled with high placebo
  response rates, had to redesign to screen and
  have a waiting period to find subjects that did
  not respond to psychoeducation and supportive
  care
• Emslie (1997) 1st study showing SSRI efficacy
  for adol depression (fluoxetine)
• 58 fluoxetine response rate vs 32 placebo
• Emslie (2002) 2nd study N219 pts RCT received
  20mg fluoxetine vs placebo for 8 weeks
• 41 remission fluoxetine vs. 20 placebo

30
Medication SSRIsTreatment of Adolescents with
Depression (TADS) -JAMA 2004

• 439 adolescents with mod to severe depression
  treated with meds/CBT/PLC or medCBT 12 wks
• 71 FluoxCBT response
• 61 Fluoxetine alone
• 43 CBT
• 35 placebo
• 29 had suicidal thoughts at baseline
• By week 12, suicidal thoughts down to 10 of pts

31
Medication - SSRIs

• Emeslie (2009) escitalopram vs. plc 12 weeks
• Response rates 64.3 versus 52.9,
• Remission rates 41.6 for escitalopram and 35.7
  for placebo
• TORDIA (2008) N334 pts 12-18 who had not
  responded to 12 wks of an SSRI switched to
  another SSRI, venlafaxine or added CBT along with
  medication change
• Adding CBT gave better response rate (54.8) as
  compared to either medication change alone
• No difference between change to a different SSRI
  or venlafaxine

32
SSRIs - dosing
Medication Starting dose Dose Increments Typical target dose Usual max dose
Fluoxetine 5-10mg 10-20mg 10-20mg kids 20-40 mg teens 60mg
Sertraline Absorption increased by food 12.5 -25mg 25-50mg 50-100mg 200mg
Paroxetine Rare use in kids 5-10mg 10mg 10-20mg 40mg
Citalopram 5-10mg 10-20mg 20-40mg 60mg
Escitalopram 5-10mg 5-10mg 10-20mg 40mg
33
SSRIs - dosing

• Typically once a day dosing in adults/teens
• Morning for fluoxetine sertraline
• Evening for paroxetine, citalopram escitalopram
  
• Pre-pubertal children metabolize more quickly -
  may need twice daily dosing
• Ensure an adequate trial before changing meds,
  maximum tolerated dose for at least 4-6 weeks

34
SSRIs Common Side Effects

• Nausea and diarrhea 5HT receptors numerous in
  gut, need to titration slowly, this side effect
  remits with exposure
• Headache usually remits with time
• Agitation, impulsivity or activation 3-8 pts
• Insomnia
• Fatigue or sedation (more common w/paroxetine,
  citalopram or escitalopram)
• Sexual side effects low libido or anorgasmia

35
SSRIs Side Effects of concern

• Increased bleeding time
• Serotonin syndrome flushing, diarrhea,
  autonomic instability, muscle tremors or spasms
  confusion
• do not use with St. Johns Wort, linezolid
  (Zyvox) or MOAIs. Caution with triptan migraine
  meds, ketorolac (Toradol) or propoxyphene
  (Darvon)
• Drug-drug interactions
• SSRIs inhibit P450 system in the liver slowing
  metabolism of other meds. Inhibit conversion of
  Tylenol 3 to morphine (P450 2D6)
• Suicidal thoughts - 4 of pts

36
SSRIs - predicting remission

• 50-60 of patients get response with 1st SSRI
• 30 of patients get into remission with 1st
  medication trial
• Predictors of remission include
• FHx of depression
• Early symptom response (within 4 weeks)

37
Treatment of Adolescents with Depression (TADS)

• Follow up 5 years later N196 pts (44.6 of
  original cohort)
• By 2 years, 96.4 had achieved recovery
• Predicted by early response to meds
• By 5 years, 46.6 a recurrence

38
Medication-other

• Few studies in newer antidepressants
• Bupropion (Wellbutrin) no RCTs in youth
• Mirtazapine (Remeron) 2 negative RCTs
• Venlafaxine (Effexor) 3 negative RCTs
• Dualoxetine (Cymbalta) no RCTs in youth
• Trazadone (Desyrel)
• TCAs 11 DB-PC studies with TCAs in adolescents ?
  none more effective than placebo. Risk of
  cardiovascular adverse effect ?HR, AV block,
  ?QTc

39
Medication Summary

• Most evidence for SSRIs
• Meds considered first line
• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Escitalorpam (Lexapro)
• Treat for 6-9 months once symptoms have improved
• Goal to treat to remission (no sxs for gt 2
  months)

40
Suicide

• CDC - 17 of adolescents think about suicide each
  year
• Thoughts of death part of MDE
• 3rd leading cause of death in adolescents about
  2,000 deaths per year
• 25 decline in suicide rate in 10-19 year range
  in past decade
• Suicide attempts often impulsive in nature

41
FDA warning about SI and antidepressant meds

• FDA reviewed 23 studies with 9 different meds - gt
  4,300 youth
• NO SUICIDES in these studies
• Adverse events reporting - SI or potentially
  dangerous behavior reported by 4 of pts on meds
  vs. 2 on placebo
• 17 of 23 studies asked about SI - no new SI or
  worsening of SI, actually decreased during
  treatment

42
Meta Analysis of 27 RCTs with SSRIs

• Studies were for MDD, OCD and non-OCD anxiety
• For MDD
• NNT 10
• NNH 112
• More effective and less SEs when treating OCD or
  non-OCD anxiety

JAMA 2007
43
Suicide and SSRIs

• FDA black box warning for risk of suicide for all
  ages with ALL antidepressants
• Need to advise families about this risk and give
  crisis info
• 2004 FDA recommended
• Weekly contact the first 4 weeks
• Every other week through week 12
• As indicated after week 12

44
Suicide and SSRIs

• FDA changed black box warning from specific
  monitoring to more general one
• All patients being treated with antidepressants
  for any indication should be monitored
  appropriately and observed closely for clinical
  worsening, suicidality, and unusual changes in
  behavior, especially during the initial few
  months of a course of drug therapy, or at times
  of dose changes, either increases or decreases.

45
General advice for families regarding SI

• No firearms in home
• Limit access to medication including over the
  counter meds
• Remove access to parents medications
• Remove razors from bathroom or other sharps
• Increase supervision (e.g. keep doors open, limit
  peer contact to with adults present)
• Importance of seeking help if suicidal thoughts
  develop or worsen
• Crisis numbers (234-1234), emergency room
  resources and 911

46
What to do in the office during active monitoring
period?

• Rating scales (e.g. Child Depression Inventory,
  CES-DC or PHQ-9) to get baseline symptoms and
  track at follow up
• Mood diary
• Cognition/thought charts - negative thoughts in
  one column and a neutral thought in other column
• Prescribe pleasant activities and exercise
• Relaxation strategies

47
Emotions Thermometer

• 10___________
• 9 ___________
• 8 ___________
• 7 ___________
• 6 ___________
• 5 ___________
• 4 ___________
• 3 ___________
• 2 ___________
• 1 ___________

48
Mood Monitoring Chart list at least 1 activity
each time frame and rate mood during then using
the emotions thermometer with10 best you ever
felt and 0 the worst
Day Morning Afternoon Evening
Monday
Tuesday
Wednesday
Thursday
Friday
Saturday
Sunday
49
Common Cognitive Distortions

• Overgeneralizing - mountains from molehills Ill
  never amount to anything
• Catastrophizing this is the worst thing could
  ever happen or Ill never feel better
• Personalizing when the teacher yelled at the
  class to be quiet, it was all my fault
• Selective abstraction - focusing only on negative
  events I did not get 100 on the test, only 98
  
• Kitchen sinking gets overwhelmed as adds more
  issues to current problem

50
Thought chart
Initial negative thought Emotion rating 0-10 Neutral more realistic thought Emotion rating 0-10
I cant do anything right and Ill never amount to anything 8 I am not the best at organizing 5
Our team didn't win all because of me 7 I did not play my best tonight nor did others 4
The entire day was pointless because I got a bad grade on the Math test 9 Im disappointed in my math grade, but I did get all my homework done today 5
51
Scheduling Pleasurable Activities
Day Morning Afternoon Evening
Monday
Tuesday
Wednesday
Thursday
Friday
Saturday
Sunday
52
Things I can do to relax when upset(identify
ones that work for the youth)

• Running
• Weight lifting
• Going for a walk
• Playing a sport
• Listening to music
• Dancing
• Read
• Do a puzzle
• Crafts

• Call a friend
• Talk to someone
• Take a hot shower
• Imagine a relaxing place in my mind
• Deep slow breathing

53
Relaxation Strategies

• Deep breathing
• Inhale for count of 5 hold briefly
• Exhale for count of 5
• Repeat 5 times
• Progressive muscle relaxation
• Begin with feet, contract muscles for count of 5
  and slowly release.
• Move up the body through all muscle groups
• Meditation many CDs and Apps available

54
What to do in the office

• Use a rating scale to monitor sxs
• Mood diaries
• Cognition charts - negative thoughts in one
  column and a neutral thought in other column
• Prescribe pleasant activities and exercise
• Relaxation strategies

55
Other patterns of depression

• Dysthymia
• Depressive disorder NOS
• Adjustment disorder with depression
• Few studies for any of these

56
Dysthymia

• Depressed mood more days than not with
• Poor appetite or overeating
• Insomnia or hypersomnia
• Low energy or fatigue
• Low self-esteem
• Poor concentration or difficulty w/ decisions
• Feelings of hopelessness
• 1 year, not 2 for children (no MDE during that
  time)
• Typically start treatment with psychotherapy due
  to chronicity

57
Depressive Disorder NOS

• A pattern of depressive sxs that does not meet
  criteria for MDE or dysthymia
• Treatment highly individualized based on FHx,
  stressors, sx presentation etc.
• Examples
• Mood episodes that do not meet enough criteria
  for MDE (limited sxs)
• Mood episodes that are do not last 2 weeks, but
  recur regularly
• Depressed mood nearly every day but not yet 1
  year

58
Adjustment Disorder

• Symptom emerge in the context of a clear stressor
  
• acute or chronic stressor
• Usually treated with talk therapy
• May use meds if stressor chronic and unlikely to
  remit or not improving with therapy and stressor
  chronic

59
Child Psychiatry Access Program

• If you have questions about a patient you are
  treating, call the Child Psychiatry Access
  Program [phone] to get a free consultation
  with a child psychiatrist

60
Summary

• Major depression occurs in 8 of adolescents
• Fast, easy screening scales available for primary
  care
• Treatment begins with psychoeducation
• Mild depression can respond to support
• Moderate depression tx starts with talk therapy
  or meds. Reassess the plan at 8 wk intervals
• Severe depression treatment likely to use meds or
  combination meds therapy as first step

61
Summary

• Things that can help while waiting for referral
  or in supportive period include
• Mood monitoring charts
• Scheduling pleasant activities
• Monitoring cognitions and feelings
• Relaxation training
• SSRIs are effective medications for MDD
• Common SEs include GI upset, headache, agitation
  and sleep disturbance
• Be careful of combining with other serotinergic
  medications
• Monitor for suicidality

62
References

• Practice Parameter for the Assessment and
  Treatment of Children and Adolescents With
  Depressive Disorders. Birmaher B and Brent D. J.
  Am. Acad. Child Adolesc. Psychiatry, 2007
  46(11)1503-1526
• Treatment and Ongoing Management Guidelines for
  Adolescent Depression in Primary Care (GLAD-PC)
  II. GLAD-PC Steering Group Laraque RE
  Pediatrics 2007120e1313-e1326
• GLAD-PC Toolkit http//www.thereachinstitute.org/g
  uidelines-for-adolescent-depression-primary-care.h
  tml
• CESDC http//www.brightfutures.org/mentalhealth/pd
  f/professionals/bridges/ces_dc.pdf
• Evaluation of the PHQ-2 as a Brief Screen for
  Detecting Major Depression Among Adolescents
  Richardson LP. Pediatrics Vol. 125 No. 5 May 2010
• A double-blind, randomized, placebo-controlled
  trial of fluoxetine in children and adolescents
  with depression. Emslie GJ, Rush AJ, Weinberg WA,
  et al. Arch Gen Psychiatry 19975410311037

63
References

• Fluoxetine for acute treatment of depression in
  children and adolescents a placebo-controlled,
  randomized clinical trial. Emslie GJ,
  Heiligenstein JH,Wagner KD, et al J Am Acad
  Child Adolesc Psychiatry 20024112051215
• Fluoxetine, Cognitive-Behavioral Therapy, and
  Their Combination for Adolescents With
  Depression Treatment for Adolescents With
  Depression Study (TADS) Randomized Controlled
  Trial March J. JAMA. 2004292807-820
• Switching to Another SSRI or to Venlafaxine With
  or Without Cognitive Behavioral Therapy for
  Adolescents With SSRI Resistant Depression The
  TORDIA Randomized Controlled Trial. Brent D et
  al. JAMA. 2008 February 27 299(8) 901913.
• Escitalopram in the Treatment of Adolescent
  Depression A Randomized Placebo-Controlled
  Multisite Trial. Emslie GJ et al. J. Am. Acad.
  Child Adolesc. Psychiatry, 200948(7)721-729.
• Change in Child Psychopathology With Improvement
  in Parental Depression A Systematic Review
  Gunlicks ML and Weissman MM J. Am. Acad. Child
  Adolesc. Psychiatry, 200847(4)379-389.

64
References

• Children of Depressed Mothers 1 Year After the
  Initiation of Maternal Treatment Findings From
  the STARD-Child Study. Pilowsky DJ, et al. Am J
  Psychiatry 2008 16511361147)
• Early Prediction of Acute Antidepressant
  Treatment Response and Remission in Pediatric
  Major Depressive DisorderTao RA. J. Am. Acad.
  Child Adolesc. Psychiatry, 200948(1)71-78.
• Clinical Response and Risk for Reported Suicidal
  Ideation and Suicide Attempts in Pediatric
  Antidepressant Treatment A Meta-analysis of
  Randomized Controlled Trials Bridge JA, JAMA.
  20072971683-1696
• The Treatment of Adolescent Suicide Attempters
  Study (TASA) Predictors of Suicidal Events in an
  Open Treatment Trial Brent DA, J. Am. Acad. Child
  Adolesc. Psychiatry, 200948(10)987-996
• Pharmacotherapy for Pediatric Major Depression.
  Rongrong T, Emslie G and Mayes T, Psychiatric
  Annuals, 2010 40(4) 192-202.