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Ralph Sherman
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1 Disclosure Information I have no financial relationships to disclose. I will discuss the off label use of several depression and anxiety medications in pediatric population

2 Pediatric Depression & Anxiety The Art & the Science. Presenter Muhammad Junaid M.D Medical Director Child and Adolescent Partial Hospital Program North Shore University Health System. 10/01/2016

3 Learning Objectives At the conclusion of this activity the participant will be able to: Recognize major symptoms and risk factors of Pediatric Depression & Anxiety. Learn about different screening tools and Behavioral Checklists help to identify Pediatric Depression and Anxiety. Learn about evidence based treatment modalities.

4 Life time Prevalence of Depression National Co-morbidity Survey Adolescent Supplement. Face to Face study of 10,123 US adolescents, ages of 13 to 18 years. Modified version of WHO Composite International Diagnostic Interview Sex Age Total Severe impairme nt MDD or Dysthymia M % F % Merikangas KR et al,jaacap2010;49:

5 DSM V Criteria Sad mood Anhedonia Changes in appetite Psychomotor retardation Weight loss or gain Insomnia or hypersomnia Problems in concentration or indecisiveness Guilt Suicidal ideation or homicidal ideation

6 Screening for Adolescent Depression Comparison of Patient Health Questionnaire 9 item (PHQ-9) PHQ -A 9 items Interest or Pleasure Depressed Sleep Fatigue Appetite Psychomotor retardation Concentration. Suicidality PHQ-9 more valid Sensitivity 90% Specificity 87% Reynolds Depression Scale Good screening tool both for group settings and individual settings

7 Risk factors for Adolescent Depression History of concussion (3.3 fold increased risk) Parental job loss (2-3 % increased in suicide related behavior particularly in girls) Parental suicidal attempt (5 fold increased risk) Gassman-Pines et al Journal of Adolescent health 2014 Brent DA et al JAMA Psychiatry December 2014.

8 Major depression in Youth and Cardiovascular Disease American Heart Association Scientific Statement : Major depression in youth is a moderate risk condition for accelerated Atherosclerosis,& early Cardiovascular Disease Goldstein Bi Et al Circulation 2015

9 Depression and Disability Adjusted life years lost (DALY) Unipolar Depressive Disorders are the top most cause of DALY in Eastern Mediterranean, European, and Western Pacific regions World Health Organization

10 Top Ten Causes of Death Among Adolescents Road injury HIV/AIDS Suicide Lower respiratory infections Interpersonal violence Diarrheal diseases Drowning Meningitis Epilepsy Endocrine blood and immune disorders World Health Organization AAU Study Highlights NorthShore April 21, 2010

11 Prevalence of Suicidal Behavior Greater in Depressed Adolescents National Comorbidity Survey of 6483 adolescents Suicidal ideation: 12.1% Suicidal plans: 4.0% Suicide Attempt: 4.1% Nock MK et al Jama Psychiatry 2013:70:

12 Outcome of Adolescent Depression Outcome 3-9 years (mean 6 years) -93% full remission from index episode -53% recurrence of Depressive Disorder -79% Developed non-mood disorder (anxiety, substance use, eating disorders) -Only 15% had no subsequent depressive episode or other non-mood disorder Melvin GA et al J of Affective Disorders 2013,151:

13 FDA Approval for Acute Treatment of Major Depressive disorder Fluoxetine (three studies) ages 8-17 Escitalopram (one study) ages Emslie Gj et al J Am Academy of Child and Adolescent Psychiatry.

14 Other Controlled Pediatric Depression Trials Positive Studies Medication Ages Number of studies Citalopram 7-17 years 1 Sertraline 6-17 years 2 Wanger et al 2003, March et al 2004

15 Negative Studies Medication Ages Number of studies Citalopram Escitalopram Paroxetine Mirtazapine Nefazadone Venlafaxine March et al 2004, Wagneret et al 2003

16 Meta-Analysis of Antidepressants Trials in Youth Antidepressants Placebo Response rate 61% 50% Bridge JA, JAMA 2007:297:

17 Maintenance Treatment of Adolescent Depression Maintained response no recurrence Sertraline 38% Placebo 0 52 weeks Cheung et al J Child and Adolescent Psychopharmacology 2008:18:

18 Treatment Algorithm SSRI Different SSRI Different SSRI + CBT Switch to Venlafaxine Switch to Venlafaxine + CBT

19 Other non SSRI Antidepressants Venlafaxine (studied in TORDIA study) Bupropion (no controlled trials for pediatric depression) Selegeline Duloxetine Desvenlafaxine

20 Dosage Range SSRI Fluoxetine: mg Escitalopram: 5-20 mg Sertraline: mg (daily or divided in two dosages) Paroxetine: mg Fluvoxamine: mg Citalopram : mg Non-SSRI Venlafaxine: (both in immediate and XR form) 25 mg to 225 mg can go up to 300 mg Duloxetine: mg Buproprion: mg (additional advantage in comorbid ADHD and less sexual side effects)

21 Newer Antidepressants No efficacy data available in pediatric depression Vilazodone L-Methylfolate Ketamine Levomilancipran Vortioxetine

22 Augmentation to SSRI for Treatment Resistant Depression Atypical antipsychotics - Case series of 10 adolescents with SSRI Resistant Depression, 70% responded to augmentation with Quetiapine - Antidepressants - Buproprion, Mirtazapine - Mood stabilizer - Lithium Pathak S et al J Child and Adolescent Psychopharmacology 2005:15:

23 Do Antidepressants increase the Suicide Risk? Meta Analysis of Pediatric Major depression Antidepressants 3% Placebo 2% Bridge et al, JAMA 2007:297:

24 Alternative Treatments for Pediatric Depression Omega-3 fatty acids Vitamin D supplementation Adjunctive Vitamin C ECT (no controlled data) Repetitive TMS Bright light treatment Exercise

25 Psychological Treatments Different Psychotherapies Family-Based Interpersonal Psychotherapy CBT (Cognitive Behavioral Therapy)

26 Anxiety Disorders DSM V Separation anxiety disorder Selective mutism Specific phobia Generalized anxiety disorder Social anxiety disorder Panic disorder Agoraphobia Anxiety disorder associated with another medical condition Substance-induced anxiety disorder Unspecified anxiety disorder Other specified anxiety disorder

27 Ages of Onset of Risk Autism Spectrum disorder ADHD Anxiety Disorders Depression Bipolar disorder 0-3 years or late for Mild 4-7 years or late for mild 6-12 years 13 years and older >16 years

28 Different terms use for Anxiety Home sickness Worry warts Self conscious or shy Excessive interpersonal sensitivity Fear Apprehension Dread Worry

29 Characteristics Common to all Anxiety Disorders Hyper vigilant Reactive to novel stimuli Threat bias Avoidance coping Catastrophic reactions Parental accommodation Midline physical symptoms

30 Scales for Anxiety Broader scales with anxiety subscales Child Behavioral Checklist(CBCL) Behavioral Assessment System for Children (BASC) Multidimensional Anxiety Scale for Children (MASC) Screen for Child Anxiety Related Disorders (SCARED) Child Version & Parent Version

31 Epidemiology of Anxiety Very common disorder 8-10% Under diagnosed Undertreated Need to look for it

32 Treatment of Pediatric Anxiety Disorders Psychotherapy should be considered as part of treatment of Childhood Anxiety Disorders. Exposure based CBT has the most empirical support. 5 CBT Components: Psycho education Somatic management skills training Cognitive reconstructuring (challenging negative expectations & modifying negative self talk) Exposure methods (exposure with desensitization) Relapse prevention plans (booster sessions)

33 CBT Informed consent of pharmacotherapy is not informed with out a discussion of CBT. CBT is also the first line of treatment for mild to moderate OCD

34 Met analysis of non OCD anxiety RCT Randomized placebo controlled trials of antidepressant in youth; 6 trials ; N = 1136 Generalized anxiety disorder Sertraline to 50 mg (Rynn et al 2001) Venlafaxine to 225 mg (Rynn et al 2007) Social anxiety disorder Paroxetine to 50 mg (Wagner et al 2004) Venlafaxine to 225 mg (March et al) Social Phobia/Separation/ Generalized Anxiety disorder Fluvoxamine to 300 mg (Rupp 2001) Fluoxetine to 20 mg (Birhamer et al 2000)

35 Common side effects: GI: N/V, anorexia, drymouth, dyspepsia CNS: headache, anxiety, nervousness, agitation, insomnia, nocturnal myoclonus, tremor Sexual: anorgasmia,decreased libido, erectile difficulties in males, abnormal ejaculation in males General side effects: SSRI Side Effects asthenia, increased sweating, weightloss Uncommon and potentially serious side effects: Suicidality, hyponatremia, mania/hypomania

36 Guide for Pediatric Anxiety Disorders First Line SSRI,Venlafaxine, Duloxetine Second Line Buspirone, Benzodiazepines, TCA Third Line Mirtazapine, Gaba-ergic anticonvulsants, Propanolol, alpha agonists. Fourth Line- low dose Atypicals, Quetiapine

37 Outcome in Pediatric Anxiety Disorders Retrospective studies suggest that untreated anxiety disorders are persistent (Biederman,1997) 12 prospective studies found that have a childhood anxiety disorder increased risk of developing anxiety disorders in later childhood, adolescence, or adulthood (Costello 2003) Fluvoxamine & Fluoxetine have shown long term efficacy

38 Conclusion Depression is very disabling, prevalent and recurrent disease in adolescents Antidepressants are much more effective in preventing relapses CBT is the first line of treatment for mild to moderate anxiety in children and adolescents

#CHAIR2016. September 16 17, 2016 The Biltmore Hotel Miami, FL. Sponsored by

#CHAIR2016. September 16 17, 2016 The Biltmore Hotel Miami, FL. Sponsored by #CHAIR2016 September 16 17, 2016 The Biltmore Hotel Miami, FL Sponsored by Depression in Children and Adolescents Karen Dineen Wagner, MD, PhD University of Texas Medical Branch Galveston, TX Karen Dineen