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Jefferson B. Prince, M.D. Massachusetts General Hospital Harvard Medical School North Shore Medical Center jprince@partn

An Update and Overview of Medical Treatments for Attention Difficulties, Anxiety and Mood Disorders in Children and Adolescents. Jefferson B. Prince, M.D. Massachusetts General Hospital Harvard Medical School North Shore Medical Center jprince@partners.org.

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Jefferson B. Prince, M.D. Massachusetts General Hospital Harvard Medical School North Shore Medical Center jprince@partn

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  1. An Update and Overview of Medical Treatments for Attention Difficulties, Anxiety and Mood Disorders in Children and Adolescents Jefferson B. Prince, M.D. Massachusetts General Hospital Harvard Medical School North Shore Medical Center jprince@partners.org

  2. Approved Ages for Psychotropic Medications in Children Name Approved Age StimulantsAmphetamine >3 (ADHD) Pemoline > 6 (ADHD) Methylphenidate > 6 (ADHD) Nonstimulant Atomoxetine > 6 (ADHD) Antidepressant andClomipramine > 10 (OCD) Anti-Anxiety Medications Fluvoxamine > 8 (OCD) Doxepin > 12 Imipramine > 6 (bed-wetting) Sertraline > 6 (OCD) Fluoxetine > 7 (MDD, OCD) AntipsychoticsHaloperidol > 3 thioridazine (generic) > 2 Pimozide > 12 Risperidone & Aripiprazole > 6 (Autism), > 13 (Schz), 10-17 (Bipolar) Mood StabilizersLithium > 12 Valproic Acid > 2 (for seizures & Bipolar adults) Lamontregene > 16 (for seizures & Bipolar) Gabapentin > 12 (for seizures) Carbamazeine any age (for seizures) SOURCE: Adapted from NIMH (2000), updated 2010

  3. A Systems View of Brain Anatomy, Function, and The Mind Mindsight by Daniel Siegel, M.D.

  4. Body Regulation, Attunement, Emotional Balance, Response Flexibility, Empathy, Self-Knowing Awareness, Fear Extinction, Intuition, Morality Nine Functions of the Middle Aspect of the Prefrontal Cortex Mindsight by Daniel Siegel, M.D.

  5. Disorders of Executive Function ADHD, Schizophrenia, Traumatic Brain Injury, Mental Retardation, Autism Specrum Disorders Language & Learning Expressive Lang Receptive Lang Reading LD Math LD Written Expression LD Arousal & Motivation Dysthymia/Depression Anxiety Disorders Posttraumatic Stress Bipolar Disorders Obsessive Compulsive Substance Abuse Social-emotional Regulation Asperger’s Disorder Oppositional Defiant Disorder Conduct Disorder Tourette’s Disorder Impairments of EF involved in all of these Executive Function ImpairmentsCharacterize Most Psychiatric Diagnoses Pennington, 2002; Brown, 2005

  6. CHAOS INTEGRATION RIGIDITY Mindsight by Daniel Siegel, M.D.

  7. Psychotropic Medication Usage in Youth with Autism Spectrum Disorders Age in Yrs % of Sample Rosenbergm RE et al., (2009) J Autism Dev Disord

  8. Psychotropic Medication Usage in Youth with Autism Spectrum Disorders Age in Yrs % of Sample Stim = Stimulant; AP = Antipsychotic; AD = Antidepressant; AC = Anticonvulsant; Alpha = Alpha-adrenergic Agent Rosenbergm RE et al., (2009) J Autism Dev Disord

  9. Pharmacotherapy of Children, Adolescents and Adults with AS • Identify Primary Emotional and Behavioral Target Symptoms • Prioritize Target Symptoms • Match Target Symptoms with Medications most likely to help Hollander et al., (2003) Lancet 362 (9385): 732-734 King and Bostic (2005) Expert Opinion in Pharmacotherapy

  10. American Academy of Child and Adolescent Psychiatry Guidelines for Treatment of ADHD: Recommendation 7 The initial psychopharmacologic treatment of ADHD should be a trial with an agent approved by the Food and Drug Administration for the treatment of ADHD [MS]. Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2007;46:894-921.

  11. "Out of the misfortune of our only child has grown the purpose and the hope that from the affliction of this one life may come comfort and blessing to many suffering in like manner.” George and Helen Bradley, 1906

  12. “To see a single daily dose of benzedrine produce a greater improvement in school performance than the combined efforts of a capable staff working in a most favorable setting, would have been all but demoralizing to the teachers, had not the improvement been so gratifying from a practical viewpoint” Bradley C. Am J Psychiatry. 1937;94:577-585.

  13. Anterior Cingulate Cortex: Subdivisions Bush et al. Trends Cogn Sci. 2000.

  14. Conceptualization of Synapse With Dopaminergic Neuron(cont’d.) AMPH& MPH AMPHVesicular release Reverse transport The Brain & the Actions of Cocaine, Opiates, and Marijuana. Available at: http://www.drugabuse.gov/pubs/teaching/Teaching4.html.

  15. Medications FDA Approved for Treatment of ADHD MAS=mixed amphetamine salts; MTS=methylphenidate transdermal system; LDX=lisdexamphetamine. *recommended max daily dose. AACAP ADHD Practice Parameters. JAACAP. 2007;46:894-921.

  16. Is Sadness/Moodiness Excessive for this Student? • Center for Epidemiologic Studies-Depression (CES-D) • Childhood Depression Rating Scale (CDRS) • Child Depression Inventory (CDI) List of Available resources can be found at www.schoolpsychiatry.org

  17. Irritable mood and dysphoria (vs. sadness in adult depression) Inability to enjoy favorite activities (“bored”) Social withdrawal Blame/worthlessness/ guilt Suicidal preoccupation “Mood reactive” similar to atypical adult depression Abnormal sleep patterns (ie, nightmares) Fatigue Diminished ability to concentrate Clinical Presentation of Depressive Disorders

  18. Post-traumatic Stress Disorder Panic Disorder MajorDepression GAD Social AnxietyDisorder OCD Comorbidity with Anxiety Disorders Is the Rule in Major Depression 48%1 50% to 65%2 8%–39%5 34–70%r4,6 67%3 1Kessler et al. Arch Gen Psychiatry. 1995;2DSM-IV; 3Rasmussen. Psychopharmacol Bull. 1988; 4Van Ameringen et al. J Affect Disord. 1991; 5Brawman-Mintzer, Lydiard RB. J Clin Psychiatry. 1996; 6Stein et al. Am J Psychiatry. 2000.

  19. 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

  20. Leading causes of death for selected age groups – United States, 2004 Source: CDC vital statistics

  21. CHILD Prior Attempt(s) (lethality, Intention) Persistent Suicidal Ideation Psychiatric Disorders (Mood) Impulsive-Aggression Hopelessness PRECIPITANTS Losses Abuse (physical, sexual, bullying, victim) Conflicts Exposure (‘contagion”) Availability of Method Intoxication Suicidal Child or Adolescent FAMILY Psychopathology Hx of Attempts Hx of Abuse Lack of Protective Factors (e.g., support, cultural, religion, supervision ect) Bridge et al., (2006) J Child Psychol Psychiatry 47 (3-4): 372-394

  22. Example of Adolescent Support Card • Safety Plan (write together and rehearse) • Doctor’s Number • Therapist’s Number • ER/Hospital Numbers • Identified Support Network (Family, Pets, Friends, Church) • National Adolescent Suicide Hotline800-621-4000 • www.suicidehotlines.com/national.html

  23. Tools for Treatment of Pediatric Depressive Disorders • Psychoeducation • Psychotherapy • Pharmacotherapy

  24. Course of Depressive Disorders Remission Recovery Well Symptom Progression Relapse Relapse Recurrence Syndrome Response Improvement Treatment Phases Acute 6-12 wks Continuation 6-12 months Maintenance > 1 yr Kupfer DJ. J Clin Psychiatry 1991

  25. 38% of adult patients' initial onset of MDD was beforeage 18 46% of depressed teens experienced a MDD episode, and an additional 22% a non-mood-related psychiatric disorder between 19-23 years Smaller social circles Decreased school performance Take advantage of fewer opportunities for educationor careers Struggle with relationships Obesity, early pregnancy Impaired work, social, and family functioning during young adulthood Course and Impact of Teen Depression B Birmaher, et al. Course and outcome of child and adolescent major depressive disorder Child Adolesc Psychiatr Clin N Am 2002. 11: 619-37. PM Lewinsohn,et al. Natural course of adolescent major depressive disorder: I. Continuity into young adulthood J Am Acad Child Adolesc Psychiatry 1999. 38: 56-63. Weissman MM, et al. Depressed adolescents grown up. JAMA 1999; 281(18):1707-13. Fergusson DM, Woodward LJ. Mental health, educational, and social role outcomes of adolescents with depression. Arch Gen Psychiatry 2002; 59(3):225-31. Keenan-Miller D, et al. Health outcomes related to early adolescent depression. J Adolesc Health 2007; 41(3):256-62

  26. Education is the Foundation of Successful Treatment • Education • Clinical manifestations • Course, Duration and Prognosis • Treatment Options: Importance of Adherence • http://www.nimh.nih.gov/health/topics/depression/index.shtml • www.wordscanwork.com/ • Secure GUNS and other means • Identify available supports and how to access • Adolescent Support Card • Agree on a treatment plan (including a safety plan; consider practicing it)

  27. Discuss wellness/lifestyle changes • Strengths • Diet (Food and Media) • Breathe and Laugh and Smile • Exercise • Sleep • Participation in School/Learning Supports • Substances (e.g., caffeine, nicotine, alcohol, marijuana, others) • Motivation, goals, values & mindset • Practice Relaxation Response and/or Stress Reduction

  28. Psychological Treatments for Children & Adolescents with Depression • Supportive • Cognitive Behavioral Therapy (CBT) • Psychodynamic • Dialectical Behavioral Therapy (DBT) • Interpersonal Psychotherapy (IPT) • Family • Group Psychotherapy • Self Help Resources http://depressionbookstore.com/depression_people/teens

  29. Treatment of Depressive Disorders For children and adolescents who are not responsive to supportive psychotherapy or who have more complicated depressions, a trial with specific types of psychotherapy and/or antidepressants is indicated [CG]. Practice Parameter for the Assessment and Treatment of Children and Adolescents with Depressive Disorders JAACAP 2007 46 (11): 1503-1526

  30. FDA Approved Medications to Treat MDD

  31. FDA Approved Medications for Major Depressive Disorders in Children and Adolescents

  32. Other medications that are not FDA approved for treatment of Pediatric Depressive Disorders but may be clinically appropriate include: A variety of other antidepressant medications that are not FDA approved but may be clinically appropriate

  33. Start low, go slow After initiation of pharmacotherapy make plan for regular follow-up & emergency access Educate patient and usually family about: Delay in onset of action Possible worsening depression/anxiety/sleep Negative behavior change Discontinuation Syndrome Potential for increase in ‘Suicidality’ Symptoms of mania, hypomania & mixed episodes www.parentsmedguide.org Treatment of Depressive Disorders in Adolescents and Young Adults

  34. Possible Complications of Treatment with an Antidepressant Medication • Activation • Bipolar Switching • Celebration • Dimensional Issues/Comorbid Disorders • Evolving Psychopathology • Frontal Lobe Symptoms • Gastrointestinal Side Effects (? Growth) • Hey! And Hematological • Suicidality Walkup & Labellarte, J Child Adol Psychopharmacology 11: 1-4, 2001 Updated 2009

  35. Black Box Warning Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Drug Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Drug Name] is not approved for use in pediatric patients…. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.

  36. Suicidal Ideation and Behavior in Subject Taking Antidepressants for Psychiatric Reasons Friedman RA and Leon AC (2007) NEJM 356: 2343-2346

  37. Meta-Analysis of Overall Rate of Emergent Suicidality All Types of Antidepressants Bridge, J. A. et al. JAMA 2007;297:1683-1696.

  38. How Long to Treat? • Medications help decrease feelings and physical symptoms of Anxiety/Depression • When ill, kids think that is who they are… • When they are better, need to ‘relearn’ who they are • If they have been ill for XX years, then how long will it take to relearn? • Sometimes they don’t want to come off • Sometimes the MDs ‘forget’ • It is never ‘for the rest of your natural life

  39. How to taper off • Establish that there is a solid response and return to function for long enough… • Trial of CBT and/or self-regulation (relaxation response, Biofeedback, MBSR) • Pick a ‘best time’ for possible relapse • Did they experience discontinuation syndrome during treatment? • Take it down slowly • Watch like a hawk for a year, educate about early symptoms of relapse

  40. “…The ultimate judgment regarding the care of a particular patient must be made by the clinician in light of all the circumstance presented by the patient and his or her family, the diagnostic and treatment options available, and available resources.” Practice Parameter for the Assessment and Treatment of Children and Adolescents with Depressive Disorders JAACAP 2007 46 (11): 1503-1526

  41. Putting It All Together Child or Adolescent Patient Sleep Subs Diet Exercise Laugh Stress Reduction ADs SSRIs SNRIs Others AAP CBT IPT DBT Clarify LD 504 IEP Advocate Educational Psychological Self Medical

  42. Complementary & Alternative Treatments for Anxiety & Mood Disorders • Omega-3 Fatty Acids • Overall, the data support using omega-3 fatty acids as adjunctive treatment for depression, but appropriate dosage levels and effective omega-3 components or ratios of components need to be established. • Folate • Folate monotherapy may benefit certain depressed patients, and augmentation with folate may enhance antidepressant efficacy from treatment initiation or may convert partial and nonresponders into responders or even into remitters. Ultimately, many patients with depression may safely benefit from folate supplementation, whether or not they have abnormal folate levels, although more information is needed about using folate in depression.

  43. Complementary & Alternative Treatments for Anxiety & Mood Disorders • SAM-e • Overall, evidence supports the use of intravenous, intramuscular, and oral SAM-e in the treatment of depression, with adjunctive therapy being possibly the most advantageous use. However, additional studies are needed to support its clinical relevance. • St. John’s Wort • Current evidence does not support the efficacy of St John’s wort in major depression, and the evidence in mild/minor depression is insufficient to draw conclusions. Freeman MP., et al., J Clin Psychiatry. 2010 Jun;71(6):669-81Complementary and alternative medicine in major depressive disorder: the American Psychiatric Association Task Force report.

  44. Light Therapy • Blue Light Spectrum Check out www.CET.org Terman and Terman CNS Spectr. 2005;10(8):647-663

  45. Can Exercise Alleviate Symptoms of Depression • YES! Exercise reduces patient-perceived symptoms of depression • As monotherapy • Relieves symptoms as effectively as cognitive behavioral therapy (CBT) or pharmacologic anti-depressant therapy (SOR: B, meta-analysis) and more effectively than bright light therapy (SOR: B, meta-analysis). • Resistance exercise and mixed exercise (resistance and aerobic) work better than aerobic exercise alone (SOR: B, meta-analysis). High-frequency exercise is more effective than low-frequency exercise (SOR: B, small RCT). • "Mindful" exercise, which has a meditative focus, such as tai chi and yoga, also reduces symptoms of depression (SOR: B, systematic review of RCTs). Gill A., et al., J Fam Pract. 2010 Sep;59(9):530-1.

  46. Mean levels of intelligence stanine scores by cardiovascular fitness or muscular strength at age 18 y. Åberg M A I et al. PNAS 2009;106:20906-20911

  47. Change in cardiovascular fitness between age 15 y and 18 y predicts intelligence scores. Åberg M A I et al. PNAS 2009;106:20906-20911

  48. Vitamin D and Depression • Mixed Results • Zhao G., e al., British Journal of Nutrition(2010) results didnot show significant associations between serum concentrations of 25(OH)D and PTH and the presence of moderate-to-severe depression,major depression or minor depression among US adults. • Hoogendijk, W. J. G. et al. Arch Gen Psychiatry 2008;65:508-512

  49. Change in Social Withdrawal Over 8 Weeks in 10 Subjects With Autistic Disorder Receiving Placebo Followed by Three Escalating Doses of D-Cycloserine • N=12 children with autism • 1 dropped due to worsening sterotypic behavior • D-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamate receptor subtype, has been shown to reduce negative symptoms in adults with schizophrenia Posey et al., (2004) : Am J Psychiatry 161(11):2115-2117

  50. Supports for Children and Adolescents with Depression • American Academy of Child and Adolescent Psychiatry www.aacap.org • American Psychiatric Association www.psych.org • Education about Depression and use of antidepressants in adolescents available at www.parentsmedguide.org • Screening Tools available at www.schoolpsychiatry.org • The National Alliance on Mental Illnesswww.nami.org • A Family Guide: What Families Should Know About Adolescent Depression and Treatment Options www.nami.org/Content/ContentGroups/CAAC/Family_Guide_final.pdf • The Depression Sourcebook By Brian P. Quinn, C.S.W., Ph.D.

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