Diagnosis and Treatment of Major Depression in Adolescence

David L. Fogelson, M.D.

Clinical Professor of Psychiatry

David Geffen School of Medicine at UCLAAnd The Semel Institute for Neuroscience and Human

Behavior at UCLA

Defining Depression

DDep

Disorder

Dep Symptoms

©JR Asarnow2010

Mary• Presents with frequent school absences

• Stomach aches

• Difficulty sleeping due to stomach pain

• Missing school frequently

• Sad nearly all the time

• Recent onset of the following symptoms

– Can’t sleep at night

– Not eating well

– Can’t concentrate at school, drop in grades

– Tired

– Feels worthless

– Thoughts of death and suicide

Is Mary suffering from:a.Major Depressionb.Dysthymic Disorderc.A depressive adjustment Disorderd.None of the aboveAnswer a.

Clinical Depression: Major DepressionDuration ≥ 2 weeks

Critical Symptoms Depressed, irritable , or anhedonic mood nearly all the time

# Symptoms- 5 of 9 symptoms must include depressed/irritable mood or anhedonia

Depressed/Irritable MoodAnhedoniaInsomnia or hypersomniaAppetitie disturbanceConcentration problems/indecisionLow energy or fatigueWorthlessness or guilt for no reasonAgitation or moves more slowly than usualThoughts of death or suicide

Severity Distress or functional impairment

EXCLUSION Not due to drugs/medication/medical disorder. Not bereavement, not a mixed episode

Diagnosis-Specific Severity Assessment: PHQ-9, symptoms in

Major Depression

David L. Fogelson, M.D., www.DavidFogelson.com, June 2013

Danny

• Getting into trouble at school

• Irritable and crabby at home, been generally unhappy for past year

• Complains of being bored all of the time

• Feels like not as good as other kids

• Can’t concentrate in school, drop in grades

• Says his life is awful, no reason to think it will get any better, feels like giving up

Does Danny suffer from:a.Major Depressionb.Dysthymic Disorderc.Bipolar Disorderd.Oppositional Defiant Disordere.None of the aboveAnswer b.

Clinical Depression: Dysthymic DisorderDuration ≥1 year for children

Critical Symptoms Depressed/ irritable mood most of the time more days than not

# Symptoms- 2 of 6 symptoms, must include depressed/irritable mood

Either overeating or lack of appetite. Sleeping too much or having difficulty sleeping. Fatigue, lack of energy. Poor self-esteem. Difficulty with concentration or decision making. Feeling hopeless.

Severity Distress or functional impairment

EXCLUSION No MDD in Year 1.Never manic/hypomanic/mixed/ cyclothymicNot due to psychosis, drugs/medication/medical disorder. Not bereavement

Ana

Presents to ER with suicide attempt, serious overdose

Boyfriend broke up with her

Hasn’t been able to stop crying since break-up 5 days ago

Feels worthless

Can’t sleep

Doesn’t feel like eating

Worried that she is pregnant, feels nauseous

Anna suffers from Major Depression. Depression isa.Extremely rare in teens, <.1% b.Rare, < 1%c.Low frequency, 1-2%d.Common, 5-6%Answer d.

Children do suffer from depressive disorders: Pediatric depression is a prevalent condition

• Rates increase with age; pattern differs by gender<13 yrs: 2.8% (+ .5)13-18 yrs 5.6% (+ .3)

• 1:1 sex ratio (or more boys) prior to adolescence• Increased frequency in girls during adolescence

13-18 yrs girls 5.9%13-18 yrs boys 4.6%

Rates approach adult prevalence by end of adolescence

After the first episode of depression remits therisk for a second episode is approximately:

a. 10%b. 30%c. 50%d. 70%

Answer c.

Pediatric Depression Not Benign Condition

Depression recurrent (in up to ~60-75% of cases), 20% have persistence >2yrs 40-60% relapse after successful treatment 70% have adult depression Episodes are lengthy: MDD (7-9 mos) in clinical cases;

Double Depression (~3yrs) Associated with significant impairment in school, with family,

and peers Suicide risk in adults with history of adolescent MDD is 5x

adults with late onset

Asarnow et al., 1994; Kovacs et al., 1984a, 1994,1997; Lewinson et al., 1994; McCauley et al., 1993; Puig-Antich et al., 1989; Rao et al., 1995; Weissman et al., 1999 a,b

Elevated rates of Suicide & Suicide Attempts in Adolescent-Onset MDD by

Early Adulthood

From Weissman et al. (1999). Depressed Adolescents Grown Up. JAMA Mean age at follow-up 26 yrs, follow-up period ≈10 years

Comorbidity/Co-Occurring Disorders: High Across Range of Disorders

Most youths present with another diagnosis, ~80-90%40-50% have an anxiety disorder, anxiety disorders often

precede the onset of depressive disordersDouble depression common, ~ 20% DD/MDDADHD comorbid in ~ 20%Conduct disorder in ~ 50% of school age depressives Increased risk for bipolar disorder (8%-49%)

Common overlap with PTSD, OCD

Baji et al., in press; Biederman et al., 1995; Carlson & Kashani, 1988; Ferro et al., 1994; Fombonne et al., 2001; Geller et al., 2001; Goodyer et al., 1997; Kovacs et al., 1988/89, 1994, 1997 and Unpub; McCauley et al., 1993; Mitchell et al., 1988; Rao et al., 1995; Ryan et al., 1987; Shain et al., 1991; Strober & Carlson, 1982; Strober et al., 1993; Weiss & Garber, 2003; Weissman et al., 1999a,b

TREATMENT

Do we have effective treatments?

Treatment for Depression in Children and Adolescents

• Psychotherapy

• Pharmacotherapy

• Combination psychotherapy and pharmacotherapy

Studies in Children and Adolescents indicate that the mostEffective treatment for Depression is:a.Psychotherapyb.Pharmacotherapyc.Combination Psychotherapy and Pharmacotherapyd.None of the above are better than placebo answer c.

• Fluoxetine 41%

• Placebo 20%

Fluoxetine Treatment for Depression in Children and Adolescents

Remission Rates

p<0.01; Emslie GJ, Heiligenstein JH, Hoog S, et al. J Am Acad Child Adolesc Psychiatry. 2000

Drug Treatments for Child and Adolescent Depression: Levels of Evidence

Short-Term Efficacy

FluoxetineSertralineFluvoxamineParoxetineCitalopram/Escitalopram TCAsVenlafaxineDuloxetine

ABCB

A *CBC

A = >2 randomized, controlled studies; B = 1 randomized, controlled study; C = Clinical experience (open studies, case reports, etc)*-- fluoxetine FDA approved for depression ≥ 8 yrs; Escitalopram > 12-17.Adapted from Jobson KO, Potter WZ. Psychopharmacol Bull. 1995;31:457–459.

*

Adapted from McCracken, 2009

Because medspose a risk for suicide, they should:a.Never be prescribedb.Monitored carefully duringthe first month of treatmentc.Avoided in BipolarDepressiond.B & C are correctAnswer d.

FDA Public Health AdvisoryMarch 2004

Today the Food and Drug Administration (FDA) directed manufacturers of all antidepressant drugs to revise the labeling for their products to include a boxed warning and expanded warning statements that alert health care providers to an increased risk of suicidality (suicidal thinking and behavior) in children and adolescents being treated with these agents, and to include additional information about the results of pediatric studies.

Suicidality in Children and Adolescents Suicidality in Children and Adolescents Treated With Antidepressant MedicationsTreated With Antidepressant Medications

What kind of depression treatment do teens prefer?

Wait & Watch

Therapy

Medication

21%

52%

27%

Jaycox, L.H., Asarnow, J.R, Sherbourne, C.D., et al. (2006). Adolescent Primary Care Patients’ Preferences for Depression Treatment. Administration and Policy in Mental Health 33, 198-207. © Joan R. Asarnow for YPIC Team

Cognitive Behavior Therapy (CBT)

• Established psychosocial treatment for adolescent depression with evidence based supporting efficacy

• Acute treatment studies demonstrate greater efficacy for CBT (12-16 sessions) as compared to alternative psychosocial interventions and waitlist conditions

• Response rates for CBT appear to be between 60-66% (vs. 38-48% in comparison conditions)

• Although we focus on CBT today, there are accumulating data supporting other psychotherapies (e.g. IPT)

Psychotherapy Trial: MDD Remission (No MDD + BDI <9 for 3 Weeks)

0

10

20

30

40

50

60

CBT (N=35) Family (N=31)Supportive (N=33)Overall p=0.05; CBT vs. family p=0.03; CBT vs. supportive p=0.04Brent DA, Holder D, Kolko D, et al. Arch Gen Psychiatry. 1997(Sep);54(9):877-885

Courtesy, McCracken, 2009

71%61%

43%35%

0

20

40

60

80

100

COMB FLX CBT PBO

Adolescent DepressionCombined CBT + Medication Treatment of Choice for

Moderate to Severe Major Depression

N=439, Treatment of Adolescent Depression Study (TADS); Week 12 Acute Treatment Response

Kennard et al. Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS). J Am Acad Child Adolesc Psychiatry. 2006 Dec;45(12):1456-60

TADS Recovery Incomplete: Remission Rates are Low & 50% of Remitted Youths Had Residual

Symptoms

*CDRS-R total score ≤28 as the criterion for remission. COMB> FLX,CBT, PBO, P=.0009; FLX=CBT=PBO

6-Site NIMH StudyMH61835 Pittsburgh, Brent MH61864 UCLA, Asarnow MH61856 Galveston, WagnerMH61869 Portland, Clarke MH61958 Dallas, EmslieMH62014 Brown, Keller

334 outpatient adolescents, ages 12-17 years, with diagnosis of major depressionDepression persists despite at least 6 weeks of SSRI treatmentAcute phase 12-week trial

JAMA Feb 27, 2008

TORDIA Supports Value of CBT-Clinical Response by Treatment Group

0

10

20

30

40

50

60

70

80

Treatment Group

SSRI

SSRI & CBT

VLX

VLX & CBT

%

CBT vs none, 54.8% vs 40.5%, p<0.009

N= 334

JAMA Feb 27, 2008