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

Defining Depression D Dep Symptoms Dep Disorder ©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: Major Depression Dysthymic Disorder A depressive adjustment Disorder None of the above Answer a.

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

Danny Getting into trouble at school Does Danny suffer from: Major Depression Dysthymic Disorder Bipolar Disorder Oppositional Defiant Disorder None of the above Answer b. 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

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 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 is Extremely rare in teens, <.1% Rare, < 1% Low frequency, 1-2% 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 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 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 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: Psychotherapy Pharmacotherapy Combination Psychotherapy and Pharmacotherapy 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 A * * Because meds pose a risk for suicide, they should: Never be prescribed Monitored carefully during the first month of treatment Avoided in Bipolar Depression 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? 21% 27% 52% 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) 60 50 40 30 20 10 CBT (N=35) Family (N=31) Supportive (N=33) 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

6-Site NIMH Study MH61835 Pittsburgh, Brent MH61864 UCLA, Asarnow MH61856 Galveston, Wagner MH61869 Portland, Clarke MH61958 Dallas, Emslie MH62014 Brown, Keller 334 outpatient adolescents, ages 12-17 years, with diagnosis of major depression Depression persists despite at least 6 weeks of SSRI treatment Acute phase 12-week trial JAMA Feb 27, 2008

TORDIA Supports Value of CBT-Clinical Response by Treatment Group % JAMA Feb 27, 2008 CBT vs none, 54.8% vs 40.5%, p<0.009