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Depression in Childhood and Adolescence

Depression in Childhood and Adolescence. Alan Apter M.D Feinberg Child Study Center Schneider Children’s Medical Center. DEPRESSION IS AN INTERNALIZING DISORDER. DEPRESSION IS AN INTERNALIZING (VS EXTERNALIZING) DISORDER IS VERY MUCH UNDERDIAGNOSED

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Depression in Childhood and Adolescence

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  1. Depression in Childhood and Adolescence Alan Apter M.D Feinberg Child Study Center Schneider Children’s Medical Center

  2. DEPRESSION IS AN INTERNALIZING DISORDER • DEPRESSION IS AN INTERNALIZING (VS EXTERNALIZING) DISORDER • IS VERY MUCH UNDERDIAGNOSED • THE DIAGNOSIS AND EARLY DETECTION OF INTERNALIZING DISORDERS IS A MAJOR PUBLIC HEALTH PROBLEM

  3. SYMPTOMS(1) • Either depressed mood or loss of interest or pleasure • In children or adolescents, an irritable mood may suffice for the depressed mood criterion

  4. SYMPTOMS(2) • Significant weight loss or marked change in appetite may be substituted by a failure to make expected weight gains in children or adolescents

  5. Major Depression • Sad mood, boredom, anhedonia, irritability • Sleep changes • Appetite changes • Decreased concentration • Decreased motivation • Social withdrawal • Guilt • Suicidal ideation and behavior • Functional impairment

  6. Related Forms of Depression • Dysthymic Disorder • Double Depression • Psychotic Depression • Bipolar Depression

  7. PROBLEMS • NON-DEVELOPMENTAL PHENOTYPE • NON SPECIFIC PHENOTYPE • NEED FOR ENDOPHENOTYPE • BIOLOGICAL • COGNITIVE • ENVIRONMENTAL

  8. Epidemiology

  9. Course • Episode length 6-8 months • Risk of recurrence in 2 years-40% • Risk of recurrence in 5 years-72% • *Risk of second episode in adulthood-~100%

  10. Risk for Recurrence • Subsyndromal depression • Parent-child conflict • Greater initial severity • Abuse history

  11. Medical Treatments and Conditions • Epilepsy • Asthma • Diabetes • Thyroid disease • Migraine • Steroids • Phenobarbital • Cancer

  12. PSYCHIATRIC DIAGNOSES OF STUDY SAMPLE (n=92)

  13. FLUVOXAMINE RESPONSE IN DEPRESSIVE AND ANXIOUS PEDIATRIC ONCOLOGY PATIENTS(Gothelf et al., 2005)

  14. Selected Psychological Characteristics • Autobiographical Memory • Rumination/Distraction • Attentional Bias

  15. Selected Psychological Characteristics • Appraisal/Reappraisal • Emotional Regulation • Metacognition and Insight

  16. AUTOBIOGRAPHICAL MEMORY (Arieh, 2005)

  17. Cognitive Variables and Depression (Shorer 2005)

  18. Adverse Outcomes • School dropout • Substance and tobacco abuse • Bipolar disorder • Personality disorder • Suicidal behavior

  19. Bipolar Disorder • 10-20% of early-onset depression develop bipolar disorder • Family loading for bipolar disorder and mood disorders • Psychotic depression • Hypersomnia/hyperphagia • Hypomanic response to antidepressants

  20. Bipolar prevalence: two examples • Riverview Hospital Donovan et al 2003 • 2000: 8/231 (4%) • 2001: 28/211 (14%) • 2.5-fold increase • Marketscan Martin & Leslie 2003 • 1997: 206/17,230 (1.2%) • 2000: 474/26,006 (1.8%) • 56% increase

  21. Narrow Hallmark symptoms Full duration of episodes Intermediate Irritable (hypo)mania Short (<3 days) Broad Mood and behavior disregulation Robbins & Guze, circa 2003 Clinical description Laboratory / Neurophysiology Delimitation Outcome studies Genetics and family aggregation Treatment response??? Clinical Phenotypes of Juvenile ManiaLiebenluft, Charney, Towbin & Pine, AJP 2003

  22. Treatment • Acute treatment-12 weeks • Achievement of remission-12 weeks • Continuation treatment-6+ months • Maintenance-for those with recurrent or chronic disorder

  23. Efficacious Treatments for Child and Adolescent Depression Type of TreatmentResponse Rate Cognitive behavior therapy 54-60% Interpersonal therapy 60-75% SSRIs 60% TCAs not efficacious

  24. CBT % Clinical Remission* at End of Treatment OVERALL p = 0.05 CBT vs. SBFT p = 0.03 CBT vs. NST p = 0.04 * Clinical Remission: absence of MDD and 3 consecutive BDI scores <9 sustained through the remaining sessions Abstracted from: Brent et al., 1997: A Clinical Psychotherapy Trial for Adolescent Depression Comparing Cognitive, Family, and Supportive Therapy, Arch. Gen. Psychiatry 54:877-885

  25. Poor Response to CBT (Brent et al., 1998) • Poor functioning at intake • *Abuse • *Maternal depression • Clinical referral vs. advertisement

  26. Failure to Achieve Remission as a Function of Self-Reported Maternal Depression (BDI)* _ * Brent et al. (1998)

  27. Overall and by treatment group MDD rate (%) at the end of treatment Suicidality and its relationship to treatment outcome in depressed adolescents (28) p=.04 p=.04

  28. Response to CBT and NST as Function of History of Sexual Abuse

  29. IPTand CBT(Bronstein 2004) IPT CBT Time-limited Focused therapy Present experience Role of the therapist Cognitive-Behavioral The cognitive self Home work interpersonal The interpersonal self Without homework

  30. Dialectic Behavioral Therapy • Specific for depression associated with Borderline Personality Disorder • Heavily staff intensive • Needs replication in adults and adolescents

  31. Pharmacotherapy • SSRI treatment common • Response rate around 50-60%, often with incomplete remission • Therefore around 50% of patients will need some second intervention

  32. Concerns about safety and efficacy of SSRIs • The British Medicines and Healthcare Products Regulatory Agency (MHRA) issued a report on December 10, 2003 stating that the risk-benefit ratio for all antidepressants other than fluoxetine for adolescent depression was unfavorable. The FDA has issued a warning on March 22, 2004, but has not made as strong a statement, pending a review of the extant safety and efficacy data

  33. SSRI TREATMENT OF YOUTH MDD (Published Studies) STUDY AGE N RESULTS Emslie (1997) 8–17 97 FLX > PLB Emslie (2002) 8–17 225 FLX > PLB Keller (2001) 12–18 275 PRX > PLB = IMI Wagner (2003) 6–17 376 SRT > PLB Wagner (2004) 7–17 174 CTL > PLB 2004 August RxS37

  34. SSRI TREATMENT OF YOUTH MDD (Unpublished Industry Studies) AGENT AGE N FINDINGS Citalopram 7–17 174 CTL > PLB Citalopram 13–18 244 CTL = PLB Paroxetine 7–17 203 PRX = PLB Paroxetine 13–18 275 PRX = PLB Sertraline (6–7) (188) SRT ≥ PLB (p=.08) Venlafaxine 6–17 141 VFX = PLB Venlafaxine 6–17 193 VFX = PLB Committee on Safety of Medicines 2003 (UK) RxS39

  35. NNT=10 ES=0.23 Medications for Depressed Children: Just How Effective?

  36. David Rosenberg: Wayne State Mark Reineke: U Chicago / Northwestern Sanjeev Pathak: Cincinnati Norah Feeney: Case Western Anne Marie Albano: NYU Bruce Waslick: Columbia Paul Rohde / Anne Simmons: U Oregon Elizabeth Weller: Penn John Walkup: Hopkins Charles Casat: Carolinas Med Ctr Chris Kratochvil: Nebraska Graham Emslie: UT Southwestern TA DS

  37. TREATMENT OF TEEN DEPRESSION (TADS) (n = 439) TREATMENT % RECOVERED 95%CI SUICIDAL AE’S PLACEBO 34%, 26-44% 4 CBT 43% 34-52%5 FXT 61% 51-70% 9 CBT + FXT 71% 62-80% 6 TADS TEAM JAMA. 2004;292:807-820 RxS38

  38. Adverse Events(Kronenbrg 2005)

  39. Figure 1. Incidence of Suicide-Related AEs by Treatment and Age (Apter et al., 2005)

  40. Brent (JAMA 2007) • 5,310 children and teenagers from 27 studies. • 1/ 100 kids treated with antidepressants, experienced worsening suicidal feelings above what would have happened without drug treatment. • In contrast, the FDA analysis found an added risk affecting about two in 100 patients.

  41. Venlafaxine ER Acad Child Adolesc Psychiatry. 2007 • No significant differences between venlafaxine ER and placebo • Greater improvement on the Children's Depression Rating Scale-Revised with venlafaxine ER than with placebo (-24.4 versus -19.9; p = .022) among adolescents (ages 12-17) • not among children (ages 7-11).

  42. adverse events • Anorexia and abdominal pain. • Hostility and suicide-related events were more common in venlafaxine • No completed suicides.

  43. Conversion-By Diagnosis Severe Depression Mild Depression Anxiety

  44. Conversion-By Antidepressant Class TCA Other SSRI None

  45. Conversion-By Age Category 15-19 10-14 25-29 20-24 5-9

  46. By Age and Antidepressant Status RR 5-14 = 2.9 (2.8,3.1) RR 15-29 = 1.4 (1.3, 1.5) Exposed, 15-29 Exposed, 5-14 Unexposed, 15-29 Unexposed, 5-14

  47. PHARMACOGENETICS GENETIC STUDIES MAY ALSO ENABLE US TO PREDICT RESPONSE TO ANTIDEPRESSANT DRUGS

  48. Pharmacogenetic Data • Response rate (CGI ≤ 2) for the different genotypes. P = 0.048 at week 8

  49. Implications • According to TADS, NNT / NNH ratio is 4 • Genotyping 5-HTT costs $1 and can be done in less than 24 hours. • If carriers of the ‘ss’ genotype are not expose to SSRI, the NNT / NNH equals 6

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