Joan Rosenbaum Asarnow, Ph.D. University of California, Los Angeles Assessment of Depression & Suicide Risk: Strategies for Matching Youths to Optimal Interventions Joan Rosenbaum Asarnow, Ph.D. University of California, Los Angeles Melissa Institute Some slides adapted from M Kovacs and J. McCracken

Disclosures: Joan Rosenbaum Asarnow, Ph.D. Source Consult/Honorarium Research Grant California Institute of Mental Health Depression Treatment Quality Improvement (DTQI) Casa Pacifica CBT Training Los Angeles County DMH and sites CBT Training, DTQI Phillip Morris Unrestricted American Foundation for Suicide Prevention X NIMH SAMHSA Sanofil- Aventis Spouse

Depression

Presentation Goals Why assess depression? Review current evidence on rates of depression and course of depression in youths Do we have effective treatments for depression in youths? Review evidence supporting CBT as evidence-based practice How can we improve care for depression? Why CBT within the context of an overall Depression Treatment Quality Improvement Program

Depression Facts Over 18 million Americans are depressed As many as 2 million of these are adolescents

Defining Depression D Dep Symptoms Dep Disorder

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

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

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

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

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

THE EPIDEMIOLOGY OF YOUTH DEPRESSION: THE FINDINGS PREVELENCE/INCIDENCE NOT YET RELIABLY ESTABLISHED Age 9-16 3-mo prev. any dep d/o 2.2%a By age 16 cumulative/ predicted 9.5%a Age 14-18 (T1) lifetime major dep d/o 20.4%b Age 15-19 (T2 ) 24.0%b By age 19 prorated 28.0%b Age 18 9.4%c Age 15-16 Age 17-18 14.6%d 13.5%d aCostello et al., 2003; bLewinson et al., 1998; cReinherz et al., 1993; dKessler & Walters, 1998

Pediatric Depression Not Benign Condition Depression recurrent (in up to ~60-75% of cases), One year recurrence greater than adults (40% vs. 24%) 20% have persistence >2yrs 40-60% relapse after successful treatment 70% have adult depression Episodes are lengthy: MDD (7-9 mos) in clinical cases; DD (~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

Pediatric Depression: Associated With High Risk of Suicidality 9 year follow up of prepubertal children Kovacs et al. J Am Acad Child Adolesc Psychiatry 1993 38% of depressed youths had made attempt by age 17

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

Burden of Pediatric Depression: Additional Consequences Eventual substance use/abuse disorders: 15% to 45%a Persistence of functional impairment: social dysfunction, work difficulties, low employment rateb Depressive episode recurrence of ~60%-69% into young adulthoodc a)Geller et al., 2001; Harrington et al., 1990; Rao et al., 1995; Weissman et al., 1999 b) Fergusson & Woodward, 2002; Fombonne et al., 2001; Garber et al., 1988; Geller et al., 2001;Harrington et al., 1991; Rao et al., 1995; Weissman et al., 1999 a,b; c)Harrington et al., 1990; Weissman et al., 1999 b; Rao et al., 1995

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

INTERIM CONCLUSION Depression in children is a serious condition Course is often protracted Presentation is complicated, often with other co-occurring mental health problems While most youth recover (80%), risk of recurrence is high (around 50% or higher) Associated with long-term disorder + functional impairment, often persisting into adulthood Recent results suggest that earlier onset MDD (child and adolescent-onsets) tends to be more severe, recurrent, and impairing than later adult-onset MDD* Most adult depressions begin during childhood-adolescent years *Zisook et al., 2007;

TREATMENT Do we have effective treatments?

Treatment for Depression in Children and Adolescents Psychotherapy Pharmacotherapy Combination psychotherapy and pharmacotherapy

Fluoxetine Treatment of Major Depression Response (CGI 2) 60 50 40 30 20 10 Fluoxetine (N=48) Placebo (N=48) p=0.02; Emslie GJ, Rush AJ, Weinberg WA, et al. Arch Gen Psychiatry. 1997;54(11):1031-1037

Fluoxetine in Juvenile Depression 219 outpatients with MDD, Ages 8-17 8 week trial 20 mg CGI ≤ 2 * N=109 N=110 Emslie G et al. J Am Acad Child Adolesc Psychiatry 2002

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 * * 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.

Treatments Not So Robust? “The evidence for effectiveness of SSRIs compared with placebo in the treatment of depressive disorders in children and adolescents is far from compelling.” Cochrane 2007 Review of SSRIs and Child and Adolescent Depression Herrick SE, Cochrane Database of Sys Rev. July 18 McCracken, 2009

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)

THE STRESS SPIRAL Stressors School/Work Problems Problems with Friends Family Problems Medical Illness Losses THE STRESS SPIRAL Actions/ Behaviors Withdrawal Decreased activity Irritable with others Thoughts Negative thoughts Low self-esteem Pessimistic Hopeless Feelings Sad Crabby Don’t enjoy anything Bored

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

Interpersonal Psychotherapy (IPT) Psychosocial treatment for adolescent depression with evidence based supporting efficacy, but newer with fewer efficacy studies as compared to CBT Response rates for IPT appear to be similar to those for CBT Data support improvements in social functioning

IPT for Depressed Adolescents (IPT-A) Focuses on interpersonal relationships and roles and the ways in which a person’s current relationships and social context cause or maintain symptoms Initial 3 sessions focus on (in adolescents- client's authority in relationship to parents; the development of new interpersonal relationships; first experiences of the death of a relative or friend; peer pressure; and single-parent families) to be addressed in the remainder of therapy. Mufson L, Weissman MM, Moreau D, Garfinkel R. Arch Gen Psychiatry. 1999(Jun);56(6):573-579

IPT for Depressed Adolescents 48 adolescent outpatients, ages 12-18 years, with major depression Randomly assigned to 12-week IPT or clinical monitoring (telephone contact) Results with IPT Greater decrease in depressive symptoms Improvement in social functioning Improved problem-solving Mufson L, Weissman MM, Moreau D, Garfinkel R. Arch Gen Psychiatry. 1999(Jun);56(6):573-579

IPT: MDD Response (HDRS 6 and/or BDI 9) 80 70 60 50 Percent 40 30 20 10 IPT (N=24) Control (N=24) Mufson L, Weissman MM, Moreau D, Garfinkel R. Arch Gen Psychiatry. 1999(Jun);56(6):573-579

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: Low Remission Rates & 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 Asarnow J.R., APA, 2009, Toronto

TORDIA: Evaluate Step-2 Treatment Strategies After Step-1 SSRI Treatment SSRI response rate around 50-60%, often with incomplete remission No empirical studies to guide clinicians on the management of the roughly 50% of patients who fail to respond to initial SSRI treatment Asarnow JR, APA 2009,Toronto

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

Effectiveness Trials: Strategies for Improving Community Treatment & Services Asarnow J.R., APA, 2009, Toronto

A Randomized Controlled Trial Effectiveness of a Quality Improvement Intervention for Adolescent Depression in Primary Care Clinics: A Randomized Controlled Trial Asarnow, Jaycox, Duan, LaBorde, Rea, Anderson, Murray, Tang, Wells Journal of the American Medical Association 2005 Jan 19; 293 (3):311-319. Sponsored by the Agency for Healthcare Research and Quality (AHRQ; Joan Asarnow, PI). Additional support from UCLA- RAND Health Services Research Center (NIMH, Ken Wells, PI)

© Joan R. Asarnow for YPIC Team YPIC Goal To test an innovative model for delivering evidence based treatments for depression through primary care © Joan R. Asarnow for YPIC Team

YPIC: Participating Sites Academic Medical Centers UCLA Mattell Children’s Hospital & Satellite Clinics University of Pittsburgh Children’s Hospital Managed Care Clinics Kaiser Permanente Los Angeles Medical Center Family Practice & Pediatric Departments Sunset & East LA Sites Public Sector Clinics Ventura County Medical Center-Family Practice & Pediatrics Venice Family Clinic © Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team YPIC Design Screened in Primary Care N=4002 Eligible Screened Youth N=1034 Baseline Assessment, N=418 Randomized to Treatment N=418 UC (n=207) QI (n=211) 6-Month Follow-Up N=344 Asarnow, J.R., Jaycox, LJ, Duan, N., et al. (2005). JAMA, 2005, 293, 311-319. © Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team

Definition of Depression Positive Endorsed stem items for major depression or dysthymic disorder on CIDI, plus depressed mood for a minimum of 1 week during past month, plus CES-D ≥ 16 CES-D ≥ 24 © Joan R. Asarnow for YPIC Team

YPIC Intervention Goals To improve initiation of and adherence to evidence based treatments Psychotherapy (CBT) Antidepressant medication To support patients and parents in making choices regarding treatment with their providers To enhance the relationship between the youth, parents, and primary care provider To test the intervention under real-world practice conditions © Joan R. Asarnow for YPIC Team

Intervention Components Provider education Care managers to support primary care clinicians and provide cognitive-behavior therapy in primary care clinics Patient & family education Emphasis on patient, parent and provider choice Local expert teams to tailor the depression management model to each system © Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team Screener indicates high levels of depressive symptoms Initial Patient Visit with Care Manager (45 min) Structured Evaluation Basic Patient and Family Education Primary Care Provider (PCP, 15 min) Develop PCP Management Plan Consider specialty mental health consultation Psychotherapy is prescribed CBT is initiated and primary care/CM follow-up arranged Follow-up visits/phone calls by CM and/or clinicians Medication or Medication + psychotherapy is prescribed Patients not started on treatment CM Follow-Up © Joan R. Asarnow for YPIC Team

A Randomized Controlled Trial Effectiveness of a Quality Improvement Intervention for Adolescent Depression in Primary Care Clinics: A Randomized Controlled Trial Asarnow JR, Jaycox L, Duan N, et al. Journal of the American Medical Association 2005 Jan 19; 293 (3):311-319. © Joan R. Asarnow for YPIC Team

Strict Inclusion/Exclusion Criteria Heterogeneous Minimal Exclusions Study Elements Efficacy TADS, TORDIA Effectiveness YPIC Dissemination CIMH Partnership Sample Selected Strict Inclusion/Exclusion Criteria Heterogeneous Minimal Exclusions Usual patient population Setting Lab Usual clinics Usual Clinic Providers Research Usual Trained + QA Treatment Structured, Manual driven Guidelines, resources, manuals, algorithms, complex treatment decisions, evidence informed Guidelines, resouces, manuals, algorithms, complex treatment decisions, evidence informed Choice None, randomized Enhanced , patient and provider choice Enhanced, Provider choice Financing Study supported Enhanced by study resources Usual © Joan R. Asarnow

Demographic characteristics of subjects at baseline Total UC QI Female 78% 77% 79% Age, Mean Yrs. 17 Ethnicity: African American 13% 14% Asian 1% .5% 2% Caucasian 12% 11% Hispanic/Latino 56% 55% 57% Mixed 15% Other 3% © Joan R. Asarnow for YPIC Team

Demographic characteristics of subjects at baseline Total UC QI At least 1 parent employed 89% 88% Language other than English at home 64% 62% 67% Baseline Depression Status: (CIDI Diagnosis) Diagnosis of Depression 43% 41% 44% Major Depression 42% Dysthymia 2% MHI-5 score, mean 19.2 19.5 18.9% MCS-12 score, mean 38.5 39.5 37.5 Externalizing Symptoms/ conduct problems, YSR T>63 28% 27% 29% © Joan R. Asarnow

Demographic characteristics of subjects at baseline Total UC QI Patients endorsing >2 PTSD symptoms 22% 25% 19% POSIT-defined substance use, problematic 27% 23% Suicidal Ideation, YSR item score>0 29% Suicide attempts/deliberate self-harm, YSR item score >0 for suicidal ideation and deliberate self-harm 13% 12% 14% © Joan R. Asarnow for YPIC Team

© Joan Asarnow for YPIC Team 2008 Depression Outcomes: Lower Rates of Severe Depression in QI vs. UC Group 42% % CES-D > 24 31% © Joan Asarnow for YPIC Team 2008

Between Group Difference Satisfaction with mental health care* Mental Health & Quality of Life Outcomes: Greater Improvement in QI vs. UC Group QI UC Between Group Difference Significance P MCS-12 44.6 42.8 2.6 (0.3 to 4.8) 2.19 .03 Satisfaction with mental health care* 3.8 3.5 0.3 0.1 to 0.5) 2.92 .004 *0-5 scale ranging from very dissatisfied (0) to very satisfied (5) © Joan R. Asarnow for YPIC Team

YPIC Intervention Associated With >50% Reduction in Suicide Attempt Rates Baseline 6-Months QI 14.2% 6.4% UC 11.6% 9.5% © Joan Asarnow for YPIC Team 2008

Mental Health Care: Higher Rate in QI Group vs. UC© Joan R Mental Health Care: Higher Rate in QI Group vs. UC© Joan R. Asarnow for YPIC Team QI UC OR P Any specialty mental health care 32% 17% 2.8 (1.6 to 4.9) <.001 Any psychotherapy/ counseling 21% 2.2 (1.3 to 3.9) .007 Medication 13% 16% 0.9 (0.4 to 1.9) .74 Mental Health treatment by primary care physician 19% 1.2 (0.7 to 2.0) .63

Medication: No Group Differences QI UC Baseline 14% 18% 6 mos. 13% 16% © Joan R. Asarnow for YPIC Team

Psychotherapy: Higher Rate in QI Group UC Baseline 22% 23% 6 mos. 32% 21% Difference 10% -2% © Joan R. Asarnow for YPIC Team

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

Conclusions: 6 Month Outcomes A quality improvement intervention delivered in primary care settings has promise for increasing rates of care and improving youth outcomes Youth tend to prefer psychotherapy/counseling to medication and when given their choice of treatment tend to choose psychotherapy Preliminary comparisons suggest intervention effects similar to those seen in adults at 6 months using similar quality improvement model (Partners in Care, Wells et al. 2000) © Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team Effects appear similar to those in adult study (Partners in Care, Wells et al. 2000) PIC YPIC QI UC MH Care Baseline 30% 27% 20% 24% 6-Months 40% 32% 17% Difference 10% 12% -7% * Tentative comparisons due to variations across studies in procedures for deriving estimates © Joan R. Asarnow for YPIC Team

Youth vs. Adults Antidepressant medication use was lower in YPIC QI UC Medication Baseline 28% 27% 14% 18% 6-Months 35% 25% 13% 16% Difference 7% -2% -1% * Tentative comparisons due to variations across studies in procedures for deriving estimates © Joan R. Asarnow for YPIC Team

Am J Psychiatry. 2009 Sep;166(9):1002-10 Long-term benefits of short-term quality improvement interventions for depressed youths in primary care Asarnow JR, Jaycox LH, Tang L, Duan N, LaBorde AP, Zeledon LR, Anderson M, Murray PJ, Landon C, Rea MM, Wells KB Am J Psychiatry. 2009 Sep;166(9):1002-10

QI Intervention Associated With Shorter Time To First Recovery Wilcoxon X2 = 3.60, p=.058; 6-months, z=2.03, p=.042; . Mean times to first recovery were: QI 8.76 months (SE, 0.35); UC 9.65 months (SE, 0.37); diff ≈27 days. Asarnow et al, American Journal of Psychiatry, 2009

Strongest Intervention Effect Seen At 6-Months *We fit a mixed-effects logistic regression model using follow-up data at 6, 12, 18 months with regression adjustment for age, gender, ethnicity, the baseline measure for the same outcome, and study sites. \ Asarnow et al, American Journal of Psychiatry, 2009

Asarnow J.R., APA, 2009, TorontoN=418 Early Intervention Effects Shifted Youths Towards Healthier Pathways Through 18-Month Follow-Up QI-Intervention Depression 12-month Baseline 18-month 6-month (MHI-5)1 0.64(0.13) -0.01(0.08) -0.03(0.01) -0.39(0.15) -0.18(0.19) -0.01(0.01) 0.46(0.12) Early effective treatment improves longer term outcomes. Important to intervene early with a treatment that works. Asarnow et al, American Journal of Psychiatry, 2009 N=418 Asarnow J.R., APA, 2009, TorontoN=418 70

Conclusions: Longer Term Outcomes Through 18 Months Youths who benefited from the intervention at 6 months tended to do better over the course of the 18-month follow-up period Depression is a relapsing condition, 18-month data suggest some protection against relapse at 18 months among youths receiving intervention Early intervention-related improvements conferred additional long-term protection through a favorable shift in illness course through 12 and 18 months. © Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team UCLA Joan Asarnow, Ph.D. Kenneth Wells, M.D., M.P.H. Naihua Duan, Ph.D. Martin Anderson, M.D., M.P.H. Bonnie Zima, Ph.D., M.P.H. Arleen Leibowitz, Ph.D. Jeanne Miranda, Ph.D. Emily McGrath, Ph.D. Margaret Rea, Ph.D. Angela Albright, Ph.D. Michael Wilkes, M.D., M.P.H. Beth Tang, M.A. Diana Polo, B.A. James McKowen, B.A. Samantha Fordwood, M.A. Eunice Kim, Ph.D Geoff Collins, M.B.A. Rochelle Noel, B.A. Ari Stern, M.A. RAND Lisa Jaycox, Ph.D. Cathy Sherbourne, Ph.D. Michael Schoenbaum, Ph.D. Mark Schuster, MD, MPH KAISER PERMANENTE Anne LaBorde, Psy.D. Robert Zeledon, M.D. Diane Morrison, M.S.W. Jim Carter, L.M.F.T. Jan Dils, L.M.F.T. John Tsilimparis, L.M.F.T. Joan Mueller © Joan R. Asarnow for YPIC Team

© Joan R. Asarnow for YPIC Team VENTURA COUNTY MEDICAL CENTER Chris Landon, M.D. Eleanor Fritz, R.N., Ph.D. Miguel Cervantes, M.D. Ken Saum, M.S.W. Fabiola Macias, B.A., M.F.T. Arlene Altobelli, Psy.D. CHILDREN’S HOSPITAL PITTSBURGH-WPIC Pamela Murray, M.D. Frances Wren, M.D. David Brent, M.D. Kelly Kelleher, M.D. Brian McCain, M.S.W.   VENICE FAMILY CLINIC Martin Anderson, M.D., M.P.H. Michael Wilkes, M.D., M.P.H. Blanca Andres, M.D. Janeen Armm, Ph.D. Juan Carlos Aguila, M.A. STONY BROOK-STATE UNIV OF NY Gabrielle Carlson, M.D. © Joan R. Asarnow for YPIC Team

Can we improve our ability to match patients to optimal treatments? Challenge: Personalized Treatment Our current treatments leave a substantial proportion of patients with residual or full-blown depressions Can we improve our ability to match patients to optimal treatments? Can we improve patient outcomes by matching patients to the treatment strategies that are most likely to be beneficial? 74

Predictors of Poor Outcome Across Treatment Groups – Acute Treatment (TADS, TORDIA) More Chronic Depression (a) (b+) Severe Suicidal Ideation (a) (b) Comorbidity (a) Functional Impairment (a) (b) Hopelessness (a) (b) Lower Expectancies For Treatment Benefits (a) Curry J, Rohde P, Simons A et al. (2006) Predictors and Moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS). Journal of the American Academy of Child and Adolescent Psychiatry, 2006; 45: 1427-1439. (b) Asarnow, JR, Emslie, G., Clarke, G. Wagner, K, Spirito, A., Vitiello, B, Iyengar, S, Shamseddeen, W, Ritz, L, Birmaher, B, Ryan, N, Kennard, B, Mayes, T, DeBar, L, McCracken, J, Strober, M, Suddath, R, Leonard, H, Porta, G, Keller, M, Brent, D.(2009) Treatment of SSRI-Resistant Depression in Adolescents: Predictors and Moderators of Treatment Response. Journal of the American Academy of Child and Adolescent Psychiatry, 2009; 48 (3):331-340.

Additional Predictors of Poor Outcome- Step 2 Treatment (TORDIA) More Severe Depression (b) History Of NSSI (b) More Severe Family Conflict (b) Drug Use (b+, youths excluded for abuse/dep) Abuse History (b+) (b) Asarnow, JR, Emslie, G., Clarke, G. Wagner, K, Spirito, A., Vitiello, B, Iyengar, S, Shamseddeen, W, Ritz, L, Birmaher, B, Ryan, N, Kennard, B, Mayes, T, DeBar, L, McCracken, J, Strober, M, Suddath, R, Leonard, H, Porta, G, Keller, M, Brent, D.(2009) Treatment of SSRI-Resistant Depression in Adolescents: Predictors and Moderators of Treatment Response. Journal of the American Academy of Child and Adolescent Psychiatry, 2009; 48 (3):331-340.

Who Benefits the Most From Medication Treatment? Lower Depression Severity Family Discord Comorbity Similar to Overall Predictors Emslie GJ. Fluoxetine in child and adolescent depression: acute and maintenance treatment. Depression Anxiety. 1998;7:32-39. 77

Who Benefits the Most From CBT/Psychosocial Treatment? Suicidal ideation: CBT > Supportive (b) Comorbid Anxiety: CBT > Supportive (a) Abuse History: No diff (c) Maternal Depression: No diff (c) (a) Brent et al. Predictors of treatment efficacy in a clinical trial of three psychosocial treaatments for adolescent depression. J Am Acad Child Adolesc Psychiatry, 1998:;7;906-914. (b) Barbe RP, Bridge J, Birmaher B et al. Suicidality and its relationship to treatment outcome in depressed adolescents. Suicide Life Threat Behav. 2004:34:44-45 (c ) Barbe RP, Bridge J, Birmaher B et al. Lifetime history of sexual abuse, clinical presentation, and outcome in a clinical trial for adolescent depression. J Clin Psychiatry. 2004: 65:77-83.

Who Benefits the Most From CBT/Combined Treatment? Mild to moderate depression severity vs. severe Mild-Mod Severity: Combined > fluoxetine alone Severe Dep: Combined=fluoxetine alone More cognitive distortion More distortion: Combined > fluoxetine alone Income level associated with better response to CBT vs placebo 79

Moderators of CBT/Combined Treatment at Step 2 Treatment: Who Benefits the Most From Combined CBT + Medication Switch Vs. Medication Switch Alone? Significant Treatment X Baseline Variable Interaction Backward binary logistic regression, including baseline variable, medication type, CBT/combined treatment, and interaction terms.   From Asarnow J.R.,JAACAP, 2008 80

From Asarnow J.R.,JAACAP, 2009 © 2009 AACAP Greater Comorbidity Associated With Stronger CBT/Combined Treatment Effect From Asarnow J.R.,JAACAP, 2009 © 2009 AACAP 81

CBT/Combined Treatment Less Effective in Abused Youth From Asarnow J.R.,JAACAP, 2009 © 2009 AACAP 82

CBT/Combined Treatment Most Beneficial With Lower Hopelessness From Asarnow J.R.,JAACAP, 2009 © 2009 AACAP 83

Depression: Conclusions Treatments with evidence for efficacy exist Evidence-based treatments can be transported to community settings and yield improved outcomes Choice of treatment guided by youth and family preference, availability of treatments, and characteristics of youths and families

Leading causes of death for selected age groups – United States, 2004 Rank 10-14 years 15-19 years 20-29 years 30-39 years 40-49 years 50-59 years 1 Unintentional Injuries Malignant Neoplasms 2 Homicide Heart Disease 3 Suicide 4 Diabetes Mellitus 5 Congenital Malformations HIV Cerebro- vascular 6 Liver 7 Chronic Lower Respiratory Ds 8 Influenza & pneumonia Source: CDC vital statistics

Healthy People 2010 & 2020 Reducing suicide and suicide attempts in adolescents. National Health Promotion Objectives 18.1 & 18.2

Why Suicide & Suicide Attempt Prevention? Suicide is the third leading cause of death among young people ages 10-24, accounting for 4,599 deaths (MMWR, Sept. 2007, 2004 Statistics) Among 15- to 24-year olds, suicide accounts for 12.9% of all deaths annually (CDC 2005). Almost 700,000 receive medical treatment for suicide attempts

Evidence-Based Treatment: What works Evidence-Based Treatment: What works? Emergency Interventions for Suicide & Suicide Attempt Prevention

ED Visit: A Window of Opportunity to Deliver an Effective Intervention Most suicidal adolescents have substantial need for mental health services The ED visit is a major contact point for the large group of youth who receive little to no follow-up care <50% receive referrals for follow-up care (Piacentini et al., 1995; Spirito et al., 2000) A large proportion never attend any follow-up sessions (77%) and many fail to complete a full course of treatment (Rotheram-Borus et al., 1996)

Means Restriction Education: Parents Listed in Registry of Evidence-Based Suicide Prevention Programs- 1 of 4 “effective practices.” Parents informed that youth at risk for suicide and why Parents informed that risk can be reduced by restricting access to lethal means Education and problem-solving regarding how to restrict access to lethal means Kruesi, M. J. P., Grossman, J., Pennington, J. M., Woodward, P. J., Duda, D., and Hirsch, J. G. (1999). Suicide and violence prevention: Parent education in emergency department. Journal of the American Academy of Child and Adolescent Psychiatry, 38(3), 250-255. Kruesi, M. J. P., Grossman, J., and Hirsch, J. G. (1995). Five Minutes of Your Time May Mean a Lifetime to a Suicidal Adolescent. Chicago, IL: Ronald McDonald House Charities, University of Illinois—Chicago.

Specialized ED Intervention for Suicidal Adolescent Females Listed in Registry of Evidence-Based Suicide Prevention Programs (SPRC, 2/23/2005, Access at: www.sprc.org/featured_resources/ebpp/ebpp_factsheets.asp#type. ) One of 7 promising practices in evidence-based registry.

Intervention Components: Specialized ED Intervention SEDI ED Staff Training: enhance positive staff/patient interactions, reinforce importance of outpatient treatment, recognize seriousness of suicide attempts Motivational video: 20 min, facilitate linkage to outpatient treatment (highlight importance and facilitate realistic expectations) ED Crisis session: discuss video, screen for suicide risk, conduct therapy session, contract for outpatient treatment

Specialized ED Interveniton Enhanced ED Care Medical Evaluation & Clearance Mental Health Safety Evaluation & Disposition Family Support & Protective Monitoring Youth 1) Perceived support 3) Coping skills 4) Commitment safety Suicidal Adolescent ED Patient Linkage to Family CBT Treatment Based on Rotheram-Borus et al. 2000, ©Asarnow J.R., 2008

When Combined With Access To Structured Follow-up Treatment, SEDI Associated With Improved Outcomes (Rotheram-Borus et al., 2000) Improved adherence to recommendation for follow-up treatment Youth reported less suicidal ideation and depression at post-discharge assessment Attended more follow-up treatment sessions At 18 months, youth less depressed, mothers reported higher family cohesion

Evidence-Based Treatment: What works Evidence-Based Treatment: What works? Outpatient Treatments for Suicide & Suicide Attempt Prevention

Multisystemic Therapy (MST): Adaptation for youth in psychiatric crisis (intensive family and community based treatment, Huey et al., 2004, Henggeler et al., 2003) Intensive community based treatment aimed at mobilizing protective factors and reducing risk factors in the youth’s ecological context Based on “fit analysis” identifying risk and protective factors for individual youth Focuses on multiple systems- youth’s ecological niche (family, peers, school, community) Assisting responsible adults in the natural environment to monitor and provide structure in a manner that is likely to reduce risk for suicide More effective than emergency hospitalization and usual services at reducing rates of suicide attempts, mental health symptoms, and out of home placements and improving school attendance and family functioning

Brief home based family intervention (Harrington et al., 1998) Components In home Family problem-solving Intervention (plus UC) associated with reductions in suicidal ideation at 2 and 6 month follow-up, relative to UC alone Intervention effect not evident among youth with MDD

Cognitive Therapy (Beck, Brown et al) Suicidal behavior is the primary target of treatment Maladaptive cognitions seen as the primary pathway to suicidal behavior Treatment includes a set of cognitive-behavioral interventions including: Crisis plan Cognitive conceptualization of the suicide attempt Coping cards Hope box Relapse prevention task Developed by Aaron T. Beck and colleagues at the University of Pennsylvania

Cognitive Therapy: Results A randomized controlled trial showed that participants in the CT group had an approximately 50% lower reattempt rate at 18-month follow-up than those in Usual Care. The CT group had lower rates of self-reported depression and hopelessness across the 18-month follow-up period (Brown et al., JAMA, 2005).

Dialectical Behavior Therapy (DBT) A cognitive behavioral treatment program developed to treat suicidal clients meeting criteria for Borderline Personality Disorder Directly targets (1) suicidal behavior, (2) behaviors that interfere with treatment delivery, and (3) other dangerous, severe, or destabilizing behaviors.

Biosocial Theory of BPD Biological Dysfunction in the Emotion Regulation System Invalidating Environment Pervasive Emotion Dysregulation BPD criterion behaviors function to regulate emotions or are a natural consequence of emotion dysregulation

DBT: Conceptualization BPD symptoms develop due to limited behavioral skills for regulating negative emotions. BPD patients are biologically predisposed to experience intense emotions which were invalidated by caregivers., resulting in individuals with BPD not learning skills for down-regulating and managing emotions. BPD symptoms are attempts to regulate emotions. DBT emphasizes behavioral interventions, such as skills training and changing reinforcers as treatment

DBT Addresses 5 functions Increasing behavioral capabilities/skills Improving motivation for skillful behavior (through contingency management and reduction of interfering emotions and cognitions) Promoting generalization of gains to the natural environment Structuring the treatment environment so that it reinforces functional rather than dysfunctional behaviors Enhancing therapist capabilities and motivation to treat patients effectively

4 Modes of Service Delivery Weekly individual psychotherapy (1 hr/wk) Group skills training (2 hrs/wk) Telephone consultation (as needed within the therapist's limits to ensure generalization) Weekly therapist consultation team meetings (to enhance therapist motivation and skills and to provide therapy for the therapists).

Survival analysis for time to first suicide attempt: DBT Group had half the rate of suicide attempts (23%) vs CTBE group (46%), NNT= 4.24 Linehan, M. M. et al. Arch Gen Psychiatry 2006;63:757-766. Hazard Ratio, 2.66, P = .005. CTBE indicates community treatment by experts Copyright restrictions may apply.

DBT for Suicidal Adolescents Rathus and Miller (2002) Subjects: Suicidal adolescents with BPD features, ages 12-19 years. Quasi-experimental design: DBT = 29, TAU = 82, pre/post treatment assessments. More severe patients assigned to DBT. DBT subjects received 12 weeks of individual and group sessions. Modifications made for adolescents: including parents in therapy and skills groups, focus on adolescent “dialectical dilemmas” (e.g., leniency v. control, autonomy v. dependence) Findings: DBT group showed fewer hospitalizations and greater treatment completion than TAU. Significant pre/post decrease within DBT group in suicidal ideation, psychiatric symptoms, and BPD symptoms. Fewer suicide attempts in DBT group, but non-significant.

Conclusions: Suicide Prevention Assessing and treating suicidal behavior/suicide risk is a major problem Promising data exist on effective treatments for suicide prevention in adults In youths, most effective treatments appear to be those that: Mobilize family and community supports Teach skills for regulating emotions

Community Partnerships: Improving Care & Developing “Effective”Treatments Easily Transportable to Community Settings Community Lab ©Asarnow J.R., 2008

Michigan- Depression Treatment Quality Improvement Project Michigan DTQI Partnership: State-wide Training in Cognitive-Behavior Therapy for Adolescent Depression Michigan- Depression Treatment Quality Improvement Project Joan Rosenbaum Asarnow Margaret Rea Kay Hodges Jim Wotring Asarnow J.R., 2008

CIMH Dissemination Project Joan Rosenbaum Asarnow Margaret Rea Bill Carter Cricket Mitchell Todd Sosna Lynne Marsenich Robert Suddath California Depression Treatment Quality Improvement Project DTQI Promote High Quality Depression Treatment CBT + Pharmacotherapy Asarnow J.R., 2008