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  1. Psychopharmacology for the IBD pediatric caregiverEva Szigethy MD, PHD Associate Professor of Psychiatry, University of Pittsburgh Director, Medical Coping Clinic, Children’s Hospital of PittsburghDirector, Visceral Inflammation and Pain (VIP) CenterDivision of Gastroenterology, Hepatology, and NutritionDecember 14, 2013

  2. Disclosure • Sources of Funding • CCFA Senior Investigator Award • NIMH R01 Grants • American Psychiatric Press Inc., Book Editor • Merck- Consultant, Advisory Board • All medication suggestions in this presentation are off-label uses unless noted otherwise.

  3. Targets for Psychotropic Medications LIFE STRESS INFLAMMATION EARLY ADVERSITY STEROIDS ILLNESSPERCEPTION GENETICS

  4. Case # 1 • 12 year old female with inactive IBD on biologics present with: • Anxiety • Depression with impaired daily functioning • Pain WHAT WOULD YOU DO?

  5. Psychotherapy!Psychotherapy!Psychotherapy!

  6. Antidepressant considerations

  7. Anxiety disorders- common complaints not always captured in anxiety disorder definitions • Excessive interpersonal sensitivity • Fear • Apprehension • Dread • Shyness • Worry • Physical complaints • Sleep problems • Eating problems • Excessive need for reassurance • Explosive outbursts • Avoidance

  8. Antidepressants in patients with IBD • Clinical reports and case series support for SSRIs, SNRIs and bupropion for depression and anxiety in adults • No randomized trials in adults or children • Recent review of EMR of 1000 IBD patients- most common antidepressants prescribed by GI and PCPs • SSRIs • SNRIs • Bupropion

  9. Serotonin Reuptake Inhibitors FDA approved for children • Approved for OCD • Clomipramine > 10 years • Fluvoxamine > 8 years • Sertraline > 6 years • Fluoxetine > 7 years • Approved for depression • Fluoxetine > 12 years • Escitalopram> 12 years • Approved for non-OCD anxiety • none

  10. SSRI Efficacy for non-OCD anxiety disorders • Separation anxiety disorder, generalized anxiety disorder, social phobia • Fluvoxamine • Fluoxetine • Specific phobia • Paroxetine • Fluoxetine • Venlafaxine • Generalized anxiety disorder • Sertraline • Venlafaxine RUPP 2001; Birmaher 2003; Walkup 2009; Wagner 2004, Beckel 2007; March 2007; Rynn 2007

  11. Anxiety Disorders • Antidepressants work well • SSRIs is medication of choice • Some data for augmentation strategies • Limited data for benzodiazepines • All psychopharmacology enhanced with psychotherapy by trained professional

  12. Dosing of SSRIs based on clinical trials • Fluoxetine up to 40 mg by week 12 • Fluvoxamine 100-150 mg by week 10 • Sertraline 100-150mg by week 8 Side Effects • Activation common 10-15% • Bipolar switch uncommon (< 1%) • GI side effects early • Easy bruising and bloody noses • Suicidality ??

  13. Citalopram Dosing • FDA: citalopram should not be used > 40 mg/day • Concern about prolongation of QT interval

  14. What to do about SSRI activation? • Education- early in treatment (24-72 hours post dose change) and usually subsides • Switch to second SSRI or non-activating antidepressant • Mirtazapine (use if + anorexia, nausea, diarrhea) • Duloxetine (use if + pain) • TCAs • Amitriptyline (3 ◦) more sedating • Nortriptyline (2◦) less sedating • Desipramine(2◦) least sedating

  15. Case #2 • 16 year old male with IBD x 4 years and depression • Active inflammation +/- • Comorbid anxiety +/- • Abdominal pain +/-

  16. Decisions for depression in pediatric IBD • If inactive IBD.......then SSRI first line • If active IBD………then bupropion first line • If severe comorbid anxiety….then SSRI alone or added to bupropion • If comorbid pain….then SNRI or low dose TCA added

  17. Pediatric Depressive Disorders (No IBD) • SSRI- first line (60% response rate) • Alternate SSRI-second line (50% response rates) • Different class of antidepressant- third line • SNRI- duloxetine (20-40 mg) • Bupropion- open trials promising; no randomized trials (150- 300mg) • Selegine (transdermal) 6mg, 9mg or 12 mg/24h • Newer antidepressants- no efficacy data in children • vilazadone, desvenlafaxine, l-methylfolate, ketamine

  18. Pediatric Depression • Early response (12 weeks) predicts remission at 24 weeks • Predictors of poor response: • More severe depression • Baseline suicidality • Anhedonia • Hopelessness • Comorbid disorders (anxiety, substance abuse) • Family conflict Emslie 2011; Goldstein 2007; Asarnow 2009; Mcmalkin 2012

  19. The Black Box Warning Gibbons, R. American J. Psychiatry 163:11, November 2006; Bridge, J. JAMA (2007) 297:15: 1683-96. • October 2004: Black Box warning for suicidality in adolescents and children • 24 Trials examined, containing 4400 children and adolescents • 9 Antidepressants included • No completed suicides in these trials • More youth on a med spontaneously reported suicidality vs. youth on placebo (4/100 vs. 2/100) • This included suicidal thoughts and behaviors but again, none of these studies had any completed suicides. • A more recent trial has shown that a decrease in the amount of SSRI use has led to an increase in the suicide rates in children and adolescents.

  20. Suicide Prevention in Depressed Children and Adolescents • Encourage home safety • Adolescents are much more likely to kill themselves with firearms • Children are much more likely to kill themselves by strangulation • Ask about suicide and watch for suicidal behavior • Monitor and ask about drug/alcohol use • Monitoring after starting antidepressant: • Weeks 1-4: weekly • Weeks 5-12: every other week • After Week 12: as clinically indicated (Q4wks?) • Bottom line is any child on an SSRI, monitor carefully especially in the beginning.

  21. SSRI Treatment Choices for Depression

  22. Patient put on high dose steroids with changes in mood (irritable, depressed)….. IBD (Auto)immune Inflammation Surge of cytokines (TNFα, IL-2, IL-6, IL-12/23,IFN-γ) Steroids Treatment Systemic corticosteroids What will you do?

  23. It depends….. • If sleep disrupted……treat sleep disturbance • If irritable/depressed…..SSRI, mood stabilizer • If concentration impaired/fatigue…. bupropion, stimulants

  24. When to consult a psychiatrist? • If suicidal/suicide plan/suicide attempt • If psychotic (steroids, delirium) • If post-traumatic stress disorder- requires intensive behavioral interventions….no magic pill. • If multiple comorbid psychiatric disorders present

  25. Comorbid psychiatric diagnoses in depressed youth with IBD (n=217) (Szigethy et al., 2013) • Generalized anxiety disorder 22% • Phobias 15% • Attention Deficit Hyperactivity disorder 16% • Oppositional Defiant Disorder 9% • Separation Anxiety Disorder 9% • Post-traumatic stress disorder 1.5% • Eating disorder 1%

  26. Augmentation Strategies…time to call a psychiatrist • Clonazepam (dose up to 4-6mg/daily) • Neuroleptics (good for OCD, comorbid tics but severe side effects) • IV clomipramine (HR, BP, EKG) IV route bypasses liver • Buspirone (though negative trial for GAD) • Lithium ( Serotonergic sensitization of brain); good for comorbid depression • Stimulants- good for SSRI induced apathy and comorbid ADHD or depression • Atomoxetine…comorbid anxiety and ADHD or if stimulants not tolerated

  27. Biopsychosocial Treatment

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