Diagnosis and Treatment of Major Depression in Adolescence

David L. Fogelson, M.D.

Clinical Professor of Psychiatry

David Geffen School of Medicine at UCLA

And The Semel Institute for Neuroscience and Human Behavior at UCLA

Mary

Clinical Depression: Major Depression

Duration	≥ 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 Mood Anhedonia Insomnia or hypersomnia Appetitie disturbance Concentration problems/indecision Low energy or  fatigue Worthlessness or guilt for no reason Agitation or moves more slowly than usual Thoughts 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

Danny

Clinical Depression: Dysthymic Disorder

Duration	≥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

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 the risk 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

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 disorders
• Double depression common, ~ 20% DD/MDD
• ADHD 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 most Effective treatment for Depression is:

• A. Psychotherapy
• B. Pharmacotherapy
• C. Combination Psychotherapy and Pharmacotherapy
• D. None of the above are better than placebo

answer c.

Fluoxetine Treatment for Depression in Children and Adolescents

Remission Rates

• Fluoxetine   41%
• Placebo       20%

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
Fluoxetine Sertraline Fluvoxamine Paroxetine Citalopram/Escitalopram TCAs Venlafaxine Duloxetine	A  * B C B A  * C B C

Because meds pose a risk for suicide, they should:

• A. Never be prescribed
• B. Monitored carefully during the first month of treatment
• C. Avoided in Bipolar Depression
• D. B & C are correct

Answer d.

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

FDA Public Health Advisory March 2004

Suicidality in Children and Adolescents Treated With Antidepressant Medications

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.

What kind of depression treatment do teens prefer?

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)

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

Courtesy, McCracken, 2009

Adolescent Depression

Combined CBT + Medication Treatment of Choice for Moderate to Severe Major Depression

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

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

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

JAMA Feb 27, 2008

TORDIA Supports Value of CBT-Clinical Response by Treatment Group

CBT vs none, 54.8% vs 40.5%,  p<0.009

JAMA Feb 27, 2008